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Faculty
412-648-3333
Office: BST3 3058
Lab Website
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Ivet Bahar - Professor and John K. Vries Chair
Ph.D. in Chemistry, Istanbul Technical Institute; B.S. and M.S. in Chemical Engineering, Bogazici U
Biomolecular systems are not static: they constantly move, change shape, and interact with each other. Understanding the mechanisms of their interactions and their binding, catalytic and allosteric signaling effects is not possible without a molecular level modeling of their collective dynamics. A major research goal in my lab is to investigate the dynamics of proteins , their collective machinery and interactions with other proteins, DNA/RNA and inhibitors/drugs at multiple scales, from molecular to cellular, using fundamental principles of physical sciences and engineering.
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(412) 648-8646
Office: BST3 3053
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Joseph C. Ayoob, PhD - Assistant Professor
Ph.D., Neuroscience, Johns Hopkins University School of Medicine; B.A. Biology, University of Pennsylvania
Research: As an experimentalist, I use molecular-genetic, biochemical, and various imaging techniques to study developmentally-regulated cell death, apoptosis, during Drosophila embryogenesis. Studying this process during the development of an organism will give us new insights into how this same process also eliminates pre-cancerous cells in the adult. Training and Outreach: To rise to the responsibility of reaching out to and training the next generation of scientists, especially at early stages of their careers, we have initiated programs to provide primary research experiences to undergraduate and high school students, which are the TECBio REU @ Pitt and the DiSCoBio Summer Academy, respectively (please see the Education page for more information on these endeavors).
Ayoob JC, Chennubhotla C. (2012). First Steps. International Innovation. 30-32.
Wu Z, Sweeney LB, Ayoob JC, Chak K, Andreone BJ, Ohyama T, Kerr R, Luo L, Zlatic M, and Kolodkin AL. (2011) "A combinatorial semaphorin code instructs the initial steps of sensory circuit assembly in the Drosophila CNS." Neuron 70, 281-98.
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(412) 648-8688
Office: 3087 BST-3
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Dipak Barua - Research Assistant Professor
Ph.D., Chemical Engineering, North Carolina State University
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(412) 648-3315
Office: BST3 3078
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Panayiotis (Takis) Benos, PhD - Associate Professor
PhD
We are interested in understanding biological phenomena. We ask biological and biomedical questions and we attempt to answer them with computational tools and statistical methods, with help from our wet lab friends and collaborators. We have ben actively involved in research on the discovery and modeling of the cis-regulatory code; modeling of gene networks from heterogeneous datasets; comparative genomics; evolution of RNA viruses; protein-DNA interactions; sequence- structure-function relationships.
Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, Macmillan M, Kahn M, Kaminski N (2012). Profibrotic Role of miR-154 in Pulmonary Fibrosis.” Am J Respir Cell Mol Biol.
Watters RJ, Benos PV, Oesterreich S. (2012). To bind or not to bind - FoxA1 determines estrogen receptor action in breast cancer progression. Breast Cancer Res. 14: 312. |
(412) 624-1223
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Jeremy Berg - Professor
Specific interactions between macromolecules are key to essentially all biological processes. Our research program has two related goals. The first is to understand the structural and chemical bases by which these specific interactions occur. The second is to understand why, biologically and evolutionarily, particular interactions have the strengths that they do. Systems of particular interest involve peroxisomal protein targeting and protein and nucleic acid interactions involving zinc-binding domains.
Namuswe F, Berg JM. (2012). Secondary interactions involving zinc-bound ligands: roles in structural stabilization and macromolecular interactions. J Inorg Biochem. 111: 146-9.
Berg JM. (2012). National Centers for Biomedical Computing: from the BISTI report to the future. J Am Med Inform Assoc. 19: 151-2. |
412-648-3120
Office: BST3 10020
Lab Website
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Robert C. “Dutch” Boltz - Research Associate Professor
Ph.D., Biophysics, Pennsylvania State University
As a new member in Cellular Systems Biology Program within the Department of Computational and Systems Biology, the Drug Discovery Institute University of Pittsburgh School of Medicine, I will utilize my expertise to develop and collaborate on novel solutions to Drug Discovery using High Content Analysis and Flow Cytometry.
Huang IC, Bailey CC, Weyer JL, Radoshitzky SR, Becker MM, Chiang JJ, Brass AL, Ahmed AA, Chi X, Dong L, Longobardi LE, Boltz D, Kuhn JH, Elledge SJ, Bavari S, Denison MR, Choe H, Farzan M. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 2011;7(1):e1001258.
Spurgers KB, Alefantis T, Peyser BD, Ruthel GT, Bergeron AA, Costantino JA, Enterlein S, Kota KP, Boltz RC, Aman MJ, Delvecchio VG, Bavari S. Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen. Mol Cell Proteomics. 2010 Dec;9(12):2690-703.
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(412)648-7776
Office: BST3 3077
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Carlos Camacho, Ph. D. - Associate Professor
Ph.D. Physics, U of Maryland, College Park; M.S. and B.S.Physics, Universidad de Chile, FCFM, Santiago
A striking set of specific and non-specific interactions encoded in the protein structure tolerates binding only to a unique substrate. My main research interests focus on modeling the physical interactions responsible for molecular recognition, and in the development of new technologies for structural prediction, their substrates and supramolecular assemblies. Any progress in these fundamental problems is bound to bring about a better understanding of how proteins work cooperatively in a cell, promoting breakthroughs in every aspect of the biological sciences.
Huang Y, Wolf S, Koes D, Popowicz GM, Camacho CJ, Holak TA, Dömling A. (2012). ChemMedChem. 7: 49-52.
Koes D, Khoury K, Huang Y, Wang W, Bista M, Popowicz GM, Wolf S, Holak TA, Dömling A, Camacho CJ. Enabling large-scale design, synthesis and validation of small molecule protein-protein antagonists. PLoS One. 7:e32839. |
(412)648-7794
Office: BST3 3081
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Chakra Chennubhotla, Ph.D - Assistant Professor
Ph.D. in Computer Science, University of Toronto; M.S. in Electrical Engineering, Pennsylvania State Univ.
Developing computational models and methods to improve the understanding of major interactions and allosteric mechanisms that underlie the proper functioning of biomolecular systems. In particular (i) developing information-theoretic concepts for determining the probabilistic rates and pathways of information flow in biomolecular systems both within multicomponent structures and at the cellular level (protein-protein interaction networks); and studying the sequence of events possibly induced by information flow; (ii) designing and interpreting FRET based experiments to explore molecular interactions and correlations and assessing their functional implications; and finally (iii) developing novel methods originating from computer vision for analyzing, refining and interpreting biomolecular images in terms of the structure, dynamics and function of the observed systems, focusing on cryo-electron microscopic measurements.
Ramanathan A, Savol AJ, Agarwal PK, Chennubhotla CS (2012). Event detection and sub-state discovery from bio-molecular simulations using higher-order statistics: Application to enzyme adenylate kinase. Proteins.
Burger VM, Chennubhotla CS. (2012). Nhs: Network-based hierarchical segmentation for cryo-electron microscopy density maps. Biopolymers. 97: SI:732-741. [JIF=2.870]
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(412) 855-4562
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Nathan Clark - Assistant Professor
Ph.D. in Genome Sciences, University of Washington
Adaptive evolution brings about genetic changes in response to new challenges such as pathogens or a new environment. Our lab exploits genetic signatures left by these adaptations to determine mechanisms of functional change in proteins. In addition, we study the coevolutionary relationships between genes to infer new genetic interactions and to inform a systems-level view of the genome. Our overarching goal is to understand how proteins and their networks change over time, and we develop novel evolutionary tools to this end.
Clark NL, Alani E, Aquadro CF. (2012) Evolutionary rate covariation reveals shared functionality and coexpression of genes. Genome Res 22(4): 714-720. pdf
Kelleher ES, Clark NL, Markow TA. 2011. Diversity Enhancing Selection Acts on a Female Reproductive Protease Family in Four Sub-Species of Drosophila mojavensis. Genetics. 187(3):865-76. pdf
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(412)-648-8171
Office: BST3 3082
Lab Website
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James R. Faeder - Associate Professor
Ph.D. in Chemical Physics, University of Colorado; A.B. in Chemistry, Harvard College
I am interested in developing mathematical models of biological regulatory processes that integrate specific knowledge about protein-protein interactions. Together with collaborators as Los Alamos National Laboratory I have developed a simulation framework called BioNetGen that allows rule-based specification of biochemical reaction networks and provides both deterministic and stochastic modeling capabilities. My current research includes the development of specific models of signal transduction and the development of new stochastic simulation algorithms that will greatly broaden the scope of models that can be developed. Other research areas include model reduction, parameter estimation and uncertainty analysis, and automated model construction from databases of protein interactions.
Smith AM, Xu W, Sun Y, Faeder JR, Marai GE. (2012). RuleBender: integrated modeling, simulation and visualization for rule-based intracellular biochemistry. BMC Bioinformatics. 13 Suppl 8:S3.
Chylek LA, Hu B, Blinov ML, Emonet T, Faeder JR, Goldstein B, Gutenkunst RN, Haugh JM, Lipniacki T, Posner RG, Yang J, Hlavacek WS. (2011). Guidelines for visualizing and annotating rule-based models. Mol Biosyst. 7: 2779-95. |
(412)383-5850
Office: BST3 9043B
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Elodie Ghedin, Ph.D. - Associate Professor
Ph.D., Molecular Parasitology, McGill University; M.S., Environmental Sciences, UQAM; B.S., Biology, McGill University
Research in our group is multidisciplinary and draws upon the tools of genomics, molecular virology, and computational biology. The questions we pursue relate to pathogen emergence and adaptation. Some of our projects include 1) determining the extent, structure and underlying mechanisms of genetic variation in influenza A viruses sampled across populations and within individual hosts; 2) metagenomics approaches for the characterization from clinical samples of viruses believed to cause chronic diseases; 3) mapping of the interactome between the nematode filaria worm and its endosymbiontic bacteria Wolbachia; 4) microbiome studies of lung diseases.
Kerr PJ, Ghedin E, Depasse JV, Fitch A, Cattadori IM, Hudson PJ, Tscharke DC, Read AF, Holmes EC (2012). Evolutionary history and attenuation of myxoma virus on two continent. PloS Pathog, Oct;8(10):e1002950.
Ghedin E, Holmes EC, Depasse JV, Pinilla LT, Fitch A, Hamelin ME, Papenburg J, Boivin G (2012). Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission. J Infect Dis. |
412-383-5915
Office: BST3 10020
Lab Website
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Albert Gough, Ph.D. - Research Associate Professor, UPDDI
My research is focused on relating in vitro cellular systems models to in vivo biological functions. Using automated high content imaging systems we are able to create cellular models with readouts that indicate a wide range of cellular functions. Alterations in function at the tissue, organ and organism level, should be related to alterations in cellular functions. However, the interactions and heterogeneity at the cellular level complicates that relationship. Presently we are building a cellular model in which to analyze cancer pathway interactions and heterogeneity. The goal is to provide an approach to developing therapies that address the fundamental heterogeneity of biological systems.
Gough AH, Giuliano KA, Taylor DL. (2012). Method for Automated Tissue Analysis. Official Gazette of the United States Patent and Trademark Office Patents. Patent: US 08114615.
Giuliano KA, Gough AH, Taylor DL, Vernetti LA, Johnston PA. Early safety assessment using cellular systems biology yields insights into mechanisms of action. J Biomolecular Screening 2010 Aug;15(7):783-97. |
(412) 383-5745
Office: BST3 3086
Lab Website
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David Koes - Research Assistant Professor
PhD, Carnegie Mellon University
My research is to develop novel computational algorithms and build full-scale systems to support rapid and inexpensive drug discovery. Our current focus is on targeting protein-protein interactions and exploiting the easily accessible chemical space of MCR chemistry. We've built several systems that enable online drug discovery, including PocketQuery, AnchorQuery, and ZINCPharmer.
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(412) 383-5743
Office: BST3 3084
Lab Website
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Timothy Lezon - Assistant Professor
Ph.D. Physics, The Pennsylvania State University
My research focuses on developing data-driven models that account for the large-scale behavior of biomolecules and biological networks.
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(412) 648-3059
Office: BST3 3059
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Hagai Meirovitch - Professor Emeritus
Ph.D., Statistical Mechanics, The Weizmann Institute of Sci; M.Sc., Nuclear Phys and B.Sc., Mathematics, The Hebrew University, Israel
Structure and function of proteins by the energetic and statistical approaches. Development of modeling of solvation, methods for calculating the entropy and the free energy of macromolecules and fluids (water), and simulation and conformational search techniques for protein systems. These methods are components of a new statistical mechanics methodology for treating flexibility applied to loops, peptides, and active sites to understand protein-protein and protein-ligand recognition processes (e.g., antibody-antigen interactions) and to analyze NMR and x-ray data of flexible molecules.
White, RP and Meirovitch, H. Free volume hypothetical scanning molecular dynamics method for the absolute free energy of liquids, J. Chem. Phys. 124, 204108 (2006)
Cheluvaraja S, Meirovitch H. Calculation of the entropy and free energy of peptides by molecular dynamics simulations using the hypothetical scanning molecular dynamics method, J. Chem. Phys. 124, 1 (2006) |
412-648-3090
Office: BST3 10045
Lab Website
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Mark E. Schurdak - Research Associate Professor
Ph.D., Pharmacology, Baylor College of Medicine
My research interests center on applying a systems biology/pharmacology approach to develop more effective drug discovery strategies that utilize integrated phenotype/function-based analysis (where all targets involved are functioning in a more physiologic relevant environment) and to better understand the molecular mechanisms that cause drugs to succeed or fail in the clinic.
Yiling L, Muller M, Smith D, Dutta B, Komurov K, Iadevaia S, Ruths D, Tseng JT, Yu S, Yu Q, Nakhleh L, Balazsi G, Donnelly J, Schurdak ME, Morgan-Lappe S, Fesik S, Ram PT, Mills GB. (2011). Kinome siRNA-phosphoproteomic screen identifies networks regulating AKT signaling. Oncogene. 30: 4567-77.
Gopalakrishnan, S.M., Teusch, N., Imhof, C., Bakker, M.H.M., Schurdak, M., Burns, D.J., and Warrior, U. Role of Rho Kinase Pathway in Chondroitin Sulfate Proteoglycan-Mediated Inhibition of Neurite Outgrowth in PC12 Cells. J. Neurosci. Res. 2008; 86:2214-2226. |
412-383-5806
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Indira Shrivastava - Research Assistant Professor
PhD
Large collective motions regulate the functional properties of glutamate transporter trimers. Jiang J, Shrivastava IH, Watts SD, Bahar I, Amara SG. (2011). PNAS USA, 108: 15141-6. PMID: 21876140
Dynamics and allosteric potential of the AMPA receptor N-terminal domain. Sukumaran M, Rossmann M, Shrivastava I, Dutta A, Bahar I, Gregor IH. (2011) EMBO J . 30, 972-82. PMID: 21317871
Mechanism of substrate release by the aspartate transporter GltPh: Insights from simulations. DeChancie J, Shrivastava IH, Bahar I. (2011) Mol. BioSyst. 7,832-842. PMID: 21161089
Enhanced dynamics of HIV gp120 glycoprotein by small molecule binding.
Shrivastava I, LaLonde JM Biochemistry. 2011 May 17;50(19):4173-83. Epub 2011 Apr 21. PMID: 21488663
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412-648-9897
Office: 10048 BST 3
Lab Website
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Andrew Stern - Research Associate Professor
Ph.D.
Mali RS, Ramdas B, Ma P, Shi J, Munugalavadia V, Sims E, Wei L, Vemula S, Nabinger SC, Goodwin CB, Chan RJ, Traina F, Visconte V, Tiu RV, Lewis TA, Stern AM, Wen Q, Crispino JD, Boswell HS, Kapur R. Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. Cancer Cell. 2011: 20(3): 357-69.
Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF, Stern AM, Mandinova A, Schreiber SL, Lee SW. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature. 2011: 475(7355): 231-4.
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412-648-9200
Office: 10045 BST-3
Lab Website
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D. Lansing Taylor - Director, UPDDI, & Professor, Comp Sys Bio
PhD
Cellular and Tissue Systems Biology in Drug Discovery
Gough AH, Giuliano KA, Taylor DL. (2012). Method for Automated Tissue Analysis. Official Gazette of the United States Patent and Trademark Office Patents. Patent: US 08114615.
Nederlof M, Watanabe S, Burnip B, Taylor DL, Critchley-Thorne R. (2011). High-throughput profiling of tissue and tissue model microarrays: Combined transmitted light and 3-color fluorescence digital pathology. J Pathol Inform. 2:50. |
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Larry Vernetti - Research Associate Professor
Ph.D., Toxicology/Pharmacology, University of Arizona; MS Toxicology, University of Arizona, B.A. Medical Technology, Oregon Health Sciences Center
The focus of my research is developing early in vitro safety assessment and in vitro ADME models to identify risky compound candidates and allowing the drug developer to focus on fewer but more likely to succeed candidates. An important part of this research is the identification of the molecular mechanism of toxicity (MOA) within the cell, and then understanding how this can be used to predict target organ toxicity. The need for such an application is clear just by considering liver toxicity as an example. Despite decades of extensive animal testing, only half of the pharmaceutics which eventually produced clinical liver toxicity showed evidence of liver damage during animal trials. Bridging this gap is a necessary step forward to developing safer and effective drugs.
Giuliano, K. A.; Gough, A. H.; Taylor, D. L.; Vernetti, L. A.; Johnston, P. A., Early safety assessment using cellular systems biology yields insights into mechanisms of action. J Biomol Screen 2010, 15, 783-797.
L Vernetti, W Irwin, KA Guiliano, A Gough, K Johnston, DL Taylor. Cellular Systems Biology Applied to Pre-Clinical Safety Testing: A Case Study of CellCiphr profiling. In: Drug Efficacy, Safety and Biological Discovery: Emerging Technologies and Tools. Eds John Elkin and Jinghai J. Xu. Jonh Wiley & Sons, Inc. 2009. |
(412) 383-5856
Office: BST3 10047
Lab Website
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Andreas Vogt - Group Leader, Small Organism Discovery, UPDDI & Associate Professor, Comp Sys Bio
Ph.D., Pharmaceutical Chemistry, M.S., Pharmacy, University of Hamburg, Germany
My major research interest is the discovery of new therapeutic agents for diseases related to cell proliferation and intracellular signaling. Specific targets of interest are the mitogen-activated protein kinase phosphatases (MKPs), cellular enzymes involved in cancer, inflammation, and myocardial ischemia that have largely eluded discovery efforts. An important part of my research is the development of analysis tools to increase information content of biological assays and to enable small molecule drug discovery in whole multicellular organisms such as zebrafish.
Li M, Chen X, Ye QZ, Vogt A, Yin XM. (2012). A high-throughput FRET-based assay for determination of Atg4 activity. Autophagy. 8: 401-412.
Soares MS, Lessa JA, Mendes IC, Da Silva JG, dos Santos RG, Salum LB, Daghestani H, Andricopulo AD, Day BW, Vogt A, Pequero JL, Rocha WR, Beraldo H. (2012). N-4-Phenyl-substitutes 2-acetylpyridine thiosemicarbazones: Cytotoxicity against human tumor cells, structure-activity relationship studies and investigation on the mechanism of action. Bioorganic & Medicinal Chemistry. 20: 3396-3409. |
(412) 383-9146
Office: BST3 3061
Lab Website
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John Vries - Associate Professor
M.D., University of California, San Francisco, CA; A.B., Princeton University, Princeton, NJ
Asymmetry in the distribution of attributes along biological sequences generates signals with characteristic frequency and phase spectra. Asymmetry in the distribution of contacts in 3-dimensional models also generates signals with characteristic spectra. In some cases, these spectra are correlated. My research attempts to predict tertiary structure from these correlations. The long term goal is go develop an alignment-independent method for protein classification. The methodologies employed include n-gram analysis, Fourier analysis, eigenfunction decomposition and all poles spectral density estimation. In related research, correlations between the periodicity of pairwise relationships in molecular dynamics simulations and the results of Gaussian network analysis are compared.
Vries JK, Munshi R, Tobi D, Klein-Seetharaman J, Benos PV, Bahar I. A sequence alignment-independent method for protein classification. Appl Bioinformatics3: 137-48 (2004).
Vries JK, Xiong, L & Bahar I. The relationship between n-gram patterns and proteins secondary structure Proteins 68: 830-838 (2007). |
412-648-3335
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Daniel M. Zuckerman - Associate Professor
The Zuckerman group develops algorithms and software to study dynamical biomolecular processes, such as conformational transitions and binding.
Mamonov A, Lettieri S, Ding Y, Sarver J, Palli R, Cunningham T, Saxena S, Zuckerman DM. (2012). Tunable, mixed resolution modeling using library-based Monte Carlo and graphics processing units. Journal of Chemical Theory and Computation. 8: 2921-2929.
Lettieri S, Zuckerman DM. Accelerating molecular Monte Carlo simulations using distance and orientation-dependent energy tables: tuning from atomistic accuracy to smoothed "coarse-grained" models. J Comput Chem. 33: 268-75. |
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