Atomic-level characterization of the structural dynamics of proteins

David E Shaw; Paul Maragakis; Kresten Lindorff-Larsen; Stefano Piana; Ron O Dror; Michael P Eastwood; Joseph A Bank; John M Jumper; John K Salmon; Yibing Shan; Willy Wriggers

doi:10.1126/science.1187409

Atomic-level characterization of the structural dynamics of proteins

David E Shaw, Paul Maragakis, Kresten Lindorff-Larsen, Stefano Piana, Ron O Dror, Michael P Eastwood, Joseph A Bank, John M Jumper, John K Salmon, Yibing Shan, Willy Wriggers

1209 Citations (Scopus)

Abstract

Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.

Original language	English
Journal	Science (New York, N.Y.)
Volume	330
Issue number	6002
Pages (from-to)	341-6
Number of pages	6
DOIs	https://doi.org/10.1126/science.1187409
Publication status	Published - 15 Oct 2010
Externally published	Yes

Access to Document

10.1126/science.1187409

Cite this

@article{d5d6210ca95a4ee793e8ef24456af757,

title = "Atomic-level characterization of the structural dynamics of proteins",

abstract = "Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.",

author = "Shaw, {David E} and Paul Maragakis and Kresten Lindorff-Larsen and Stefano Piana and Dror, {Ron O} and Eastwood, {Michael P} and Bank, {Joseph A} and Jumper, {John M} and Salmon, {John K} and Yibing Shan and Willy Wriggers",

year = "2010",

month = oct,

day = "15",

doi = "10.1126/science.1187409",

language = "English",

volume = "330",

pages = "341--6",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6002",

}

TY - JOUR

T1 - Atomic-level characterization of the structural dynamics of proteins

AU - Shaw, David E

AU - Maragakis, Paul

AU - Lindorff-Larsen, Kresten

AU - Piana, Stefano

AU - Dror, Ron O

AU - Eastwood, Michael P

AU - Bank, Joseph A

AU - Jumper, John M

AU - Salmon, John K

AU - Shan, Yibing

AU - Wriggers, Willy

PY - 2010/10/15

Y1 - 2010/10/15

N2 - Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.

AB - Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.

U2 - 10.1126/science.1187409

DO - 10.1126/science.1187409

M3 - Journal article

C2 - 20947758

SN - 0036-8075

VL - 330

SP - 341

EP - 346

JO - Science

JF - Science

IS - 6002

ER -

Atomic-level characterization of the structural dynamics of proteins

Abstract

Access to Document

Fingerprint

Cite this