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Atomistic Approaches in Modern Biology pp 319–347Cite as

PcrA Helicase, a Molecular Motor Studied from the Electronic to the Functional Level

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Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 268))

Abstract

Molecular motors are adenosine tri-phosphate (ATP) hydrolysis-driven, cellular proteins responsible for a wide variety of different tasks, such as transport, energy metabolism, and DNA processing. Their operation cycle spans a wide range of length and time scales, from the localized and fast chemical reaction in the catalytic site(s) to the large scale and much slower conformational motions involved in the motors' physiological function. From a computational point of view, this means that currently there exists no single approach capable of capturing the whole spectrum of events during molecular motor function. In the present review, we show for PcrA helicase, a molecular motor involved in the unwinding of double-stranded DNA, how a combination of computational approaches can be used to examine PcrA's function in its entirety as well as in detail. Combined quantum mechanical/molecular mechanical simulations are used to study the catalytic ATP hydrolysis event and its coupling to protein conformational changes. Molecular dynamics simulations then provide a means of studying overall PcrA function on a nanosecond time scale. Finally, to reach physiologically relevant time scales, i.e., milliseconds, stochastic simulations are employed. We show that by combining the three stated approaches one can obtain insight into PcrA helicase function.

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Abbreviations

ADP:

adenosine di-phosphate

ATP:

adenosine tri-phosphate

dsDNA:

double-stranded DNA

DNA:

deoxyribonucleic acid

MD:

molecular dynamics

MM:

molecular mechanics

nt:

nucleotide

P i :

phosphate

QM:

quantum mechanics

QM/MM:

quantum mechanical/molecular mechanical

RESP:

restrained electrostatic potential

RNA:

ribonucleic acid

SMD:

steered molecular dynamics

ssDNA:

single-stranded DNA

vdW:

van der Waals

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Acknowledgments

The molecular images in this paper were created with the molecular graphics program VMD [59]. This work is supported by grants from the National Institutes of Health PHS-5-P41-RR05969 and the National Science Foundation MCB02-34938. The authors gladly acknowledge supercomputer time provided by Pittsburgh Supercomputer Center and the National Center for Supercomputing Applications via National Resources Allocation Committee grant MCA93S028.

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Authors and Affiliations

  1. Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, IL, USA

    Markus Dittrich, Jin Yu & Klaus Schulten

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  1. Markus Dittrich
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  2. Jin Yu
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  3. Klaus Schulten
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Correspondence to Klaus Schulten .

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Markus Reiher

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© 2006 Springer-Verlag Berlin Heidelberg

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Dittrich, M., Yu, J., Schulten, K. (2006). PcrA Helicase, a Molecular Motor Studied from the Electronic to the Functional Level. In: Reiher, M. (eds) Atomistic Approaches in Modern Biology. Topics in Current Chemistry, vol 268. Springer, Berlin, Heidelberg . https://doi.org/10.1007/128_2006_086

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