ABSINTH: A new continuum solvation model for simulations of polypeptides in aqueous solutions
Andreas Vitalis,Rohit V. Pappu +1 more
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The tests reveal that the computational expense for simulations with the ABSINTH implicit solvation model increase by a factor that is in the range of 2.5–5.0 with respect to gas‐phase calculations.Abstract:
A new implicit solvation model for use in Monte Carlo simulations of polypeptides is introduced. The model is termed ABSINTH for self-Assembly of Biomolecules Studied by an Implicit, Novel, and Tunable Hamiltonian. It is designed primarily for simulating conformational equilibria and oligomerization reactions of intrinsically disordered proteins in aqueous solutions. The paradigm for ABSINTH is conceptually similar to the EEF1 model of Lazaridis and Karplus (Proteins 1999, 35, 133). In ABSINTH, the transfer of a polypeptide solute from the gas phase into a continuum solvent is the sum of a direct mean field interaction (DMFI), and a term to model the screening of polar interactions. Polypeptide solutes are decomposed into a set of distinct solvation groups. The DMFI is a sum of contributions from each of the solvation groups, which are analogs of model compounds. Continuum-mediated screening of electrostatic interactions is achieved using a framework similar to the one used for the DMFI. Promising results are shown for a set of test cases. These include the calculation of NMR coupling constants for short peptides, the assessment of the thermal stability of two small proteins, reversible folding of both an alpha-helix and a beta-hairpin forming peptide, and the polymeric properties of intrinsically disordered polyglutamine peptides of varying lengths. The tests reveal that the computational expense for simulations with the ABSINTH implicit solvation model increase by a factor that is in the range of 2.5-5.0 with respect to gas-phase calculations.read more
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Journal ArticleDOI
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Classification of Intrinsically Disordered Regions and Proteins
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Uncharacterized and uncharacterized protein segments are likely to be a large source of functional novelty relevant for discovering new biology as discussed by the authors, which is likely to lead to the discovery of novel functions as well as provide important insights into existing biological processes.
Journal ArticleDOI
Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues.
Rahul K. Das,Rohit V. Pappu +1 more
TL;DR: The design of sequences with different κ-values demonstrably alters the conformational preferences of polyampholytic IDPs, and this ability could become a useful tool for enabling direct inquiries into connections between sequence–ensemble relationships and functions of IDPs.
Journal ArticleDOI
OpenMM 4: A reusable, extensible, hardware independent library for high performance molecular simulation
Peter Eastman,Mark S. Friedrichs,John D. Chodera,Randall J. Radmer,Christopher M. Bruns,Joy P. Ku,Kyle A. Beauchamp,Thomas J. Lane,Lee-Ping Wang,Diwakar Shukla,Tony Tye,Mike Houston,Timo Stich,Christoph Klein,Michael R. Shirts,Vijay S. Pande +15 more
TL;DR: OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures that was designed to be extensible, so new hardware architectures can be accommodated and new functionality can be easily added.
Journal ArticleDOI
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains
Erik W. Martin,Alex S. Holehouse,Ivan Peran,Mina Farag,J. Jeremías Incicco,Anne Bremer,Christy R. Grace,Andrea Soranno,Rohit V. Pappu,Tanja Mittag +9 more
TL;DR: It is shown that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions, which determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature.
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