Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2016 Jun 21

PMID 27322931

Citations 14

Authors

Anna S Kamenik

Ursula Kahler

Julian E Fuchs

Klaus R Liedl

Affiliations

Soon will be listed here.

Abstract

Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance.

Citing Articles

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Tang X, Kokot J, Waibl F, Fernandez-Quintero M, Kamenik A, Liedl K J Chem Inf Model. 2023; 63(22):7107-7123.

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Enhanced sampling without borders: on global biasing functions and how to reweight them.

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Energy penalties enhance flexible receptor docking in a model cavity.

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Quoika P, Fernandez-Quintero M, Podewitz M, Hofer F, Liedl K J Phys Chem B. 2021; 125(18):4898-4909.

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X-Entropy: A Parallelized Kernel Density Estimator with Automated Bandwidth Selection to Calculate Entropy.

Kraml J, Hofer F, Quoika P, Kamenik A, Liedl K J Chem Inf Model. 2021; 61(4):1533-1538.

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