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The paradigm that the primary amino acid sequence prescribes structure and thus function has for a long time been central to the understanding of protein science. Though the theory is supported by the behaviour of most structured proteins,…

Biological Physics · Physics 2022-12-19 Rickie Xian , Sarah Rauscher

Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…

Biomolecules · Quantitative Biology 2021-12-13 F. Emil Thomasen , Kresten Lindorff-Larsen

We outline recent developments in artificial intelligence (AI) and machine learning (ML) techniques for integrative structural biology of intrinsically disordered proteins (IDP) ensembles. IDPs challenge the traditional protein…

Biomolecules · Quantitative Biology 2020-12-03 Arvind Ramanathan , Heng Ma , Akash Parvatikar , Chakra S. Chennubhotla

Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP…

Conventional molecular-dynamics (cMD) simulation has a well-known limitation in accessible time and length scales, and thus various enhanced sampling techniques have been proposed to alleviate the problem. In this paper we explore the…

Chemical Physics · Physics 2018-01-17 Hadi H. Arefi , Takeshi Yamamoto

In 1999 Wright and Dyson highlighted the fact that large sections of the proteome of all organisms are comprised of protein sequences that lack globular folded structures under physiological conditions. Since then the biophysics community…

Biological Physics · Physics 2024-09-05 Zi Hao Liu , Maria Tsanai , Oufan Zhang , Julie Forman-Kay , Teresa Head-Gordon

The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by…

Molecular Dynamics (MD) simulations are fundamental computational tools for the study of proteins and their free energy landscapes. However, sampling protein conformational changes through MD simulations is challenging due to the relatively…

Biomolecules · Quantitative Biology 2023-07-20 Diego E. Kleiman , Hassan Nadeem , Diwakar Shukla

We study the dynamics of parallel tempering simulations, also known as the replica exchange technique, which has become the method of choice for simulation of proteins and other complex systems. Recent results for the optimal choice of the…

Statistical Mechanics · Physics 2009-11-13 Walter Nadler , Ulrich H. E. Hansmann

The replica exchange molecular dynamics (REMD) approach is applied to four oligomeric peptide systems. At physiologically relevant temperature values REMD samples conformation space and aggregation transitions more efficiently than constant…

Biomolecules · Quantitative Biology 2009-11-10 M. Cecchini , F. Rao , M. Seeber , A. Caflisch

Replica exchange molecular dynamics (REMD) becomes more efficient as the frequency of swap between the temperatures is increased. Recently in [Plattner et al, J. Chem. Phys. 135, 134111 (2011)] a method was proposed to implement infinite…

Statistical Mechanics · Physics 2015-06-12 Jianfeng Lu , Eric Vanden-Eijnden

Small mechanical forces play important functional roles in many crucial cellular processes, including in the dynamical behavior of the cytoskeleton and in the regulation of osmotic pressure through membrane-bound proteins. Molecular…

Chemical Physics · Physics 2023-10-20 Yuvraj Singh , Glen M. Hocky

Fast and accurate sampling method is in high demand, in order to bridge the large gaps between molecular dynamic simulations and experimental observations. Recently, integrated tempering enhanced sampling method (ITS) has been proposed and…

Numerical Analysis · Mathematics 2018-06-22 Zhiyi You , Liying Li , Jianfeng Lu , Hao Ge

Efficient computational methods that are capable of supporting experimental measures obtained at constant values of pH and redox potential are important tools as they serve to, among other things, provide additional atomic level information…

Chemical Physics · Physics 2018-09-21 Vinícius Wilian D. Cruzeiro , Adrian E. Roitberg

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-09-18 Hyungro Lee , Heng Ma , Matteo Turilli , Debsindhu Bhowmik , Shantenu Jha , Arvind Ramanathan

The current capacity of computers makes it possible to perform simulations of small systems with portable, explicit-solvent potentials achieving high degree of accuracy. However, simplified models must be employed to exploit the behaviour…

Biomolecules · Quantitative Biology 2015-06-18 R. Capelli , C. Paissoni , P. Sormanni , G. Tiana

We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In…

Statistical Mechanics · Physics 2014-01-03 Cameron Abrams , Giovanni Bussi

Molecular dynamics (MD) simulation is widely used to study protein conformations and dynamics. However, conventional simulation suffers from being trapped in some local energy minima that are hard to escape. Thus, most computational time is…

Quantitative Methods · Quantitative Biology 2022-04-28 Hao Tian , Xi Jiang , Sian Xiao , Hunter La Force , Eric C. Larson , Peng Tao

We apply a recently developed adaptive algorithm that systematically improves the efficiency of parallel tempering or replica exchange methods in the numerical simulation of small proteins. Feedback iterations allow us to identify an…

Quantitative Methods · Quantitative Biology 2007-05-23 Simon Trebst , Matthias Troyer , Ulrich H. E. Hansmann

Intrinsically disordered proteins (IDPs) constitute a broad set of proteins with few uniting and many diverging properties. IDPs-and intrinsically disordered regions (IDRs) interspersed between folded domains-are generally characterized as…

Biomolecules · Quantitative Biology 2021-06-03 Kresten Lindorff-Larsen , Birthe B. Kragelund
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