Comparison of generalized born and poisson models: Energetics and dynamics of HIV protease

David, Laurent; Luo, Ray; Gilson, Michael K.

doi:10.1002/(sici)1096-987x(200003)21:4<295::aid-jcc5>3.0.co;2-8

Cited by 102 publications

(63 citation statements)

References 50 publications

(32 reference statements)

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“…Continuum solvent simulations of HIV-PR have been reported in the past (35). Temperature was maintained by using Langevin dynamics with a collision frequency of 1 ps Ϫ1 , the timestep was 1 fs, and all bonds to hydrogen were constrained.…”

Section: Simulations In Ambermentioning

confidence: 99%

HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations

Horn̆ák

Okur²,

Rizzo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

353

447

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We report unrestrained, all-atom molecular dynamics simulations of HIV-1 protease that sample large conformational changes of the active site flaps. In particular, the unliganded protease undergoes multiple conversions between the ''closed'' and ''semiopen'' forms observed in crystal structures of inhibitor-bound and unliganded protease, respectively, including reversal of flap ''handedness.'' Simulations in the presence of a cyclic urea inhibitor yield stable closed flaps. Furthermore, we observe several events in which the flaps of the unliganded protease open to a much greater degree than observed in crystal structures and subsequently return to the semiopen state. Our data strongly support the hypothesis that the unliganded protease predominantly populates the semiopen conformation, with closed and fully open structures being a minor component of the overall ensemble. The results also provide a model for the flap opening and closing that is considered to be essential to enzyme function.

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Section: Simulations In Ambermentioning

confidence: 99%

HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations

Horn̆ák

Okur²,

Rizzo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

353

447

View full text Add to dashboard Cite

show abstract

“…However, the computational cost of solving the PB equation remains a bottleneck to its application to protein folding and routine dynamics simulations of biomolecules, despite the progress in fast PB computational methodologies (David et al, 2000;Luo et al, 2002;Prabhu et al, 2004). The generalized Born (GB) model, inspired by the Born equation for solvation energies of ions (Born, 1920), has emerged as an efficient alternative for implicit inclusion of the electrostatic solvation energy (Dominy and Brooks, 1999;Ghosh et al, 1998;Hawkins et al, 1996;Im et al, 2003b;Lee et al, 2002Lee et al, , 2003Onufriev et al, 2000Onufriev et al, , 2002Qiu et al, 1997;Scarsi et al, 1997;Schaefer and Karplus, 1996;Spassov et al, 2002;Srinivasan et al, 1999;Still et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Peptide and Protein Folding and Conformational Equilibria: Theoretical Treatment of Electrostatics and Hydrogen Bonding with Implicit Solvent Models

Chen

Brooks

2005

Advances in Protein Chemistry

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“…a particular conformation q i ∈ C(V 1 ), the outcome of the quantity V 2 ( q i ) is basically unpredictable 6 . Illustration of the conditional-probability density function P 2|1 (V2|V1) at different V1-positions.…”

Section: Hypothesismentioning

confidence: 99%

“…In the study and simulation of complex systems, such as proteins, researchers often face the dilemma of choosing among many different ways of calculating a conceptually unique potential energy V [1][2][3][4][5][6][7]. Others tackle the problem of designing new algorithms to perform this calculation looking for the improvement of the relation between accuracy and numerical complexity [8][9][10][11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A physically meaningful method for the comparison of potential energy functions

Alonso

Echenique

2005

J Comput Chem

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In the study of the conformational behavior of complex systems, such as proteins, several related statistical measures are commonly used to compare two different potential energy functions. Among them, the Pearson's correlation coefficient r has no units and allows only semi-quantitative statements to be made. Those that do have units of energy and whose value may be compared to a physically relevant scale, such as the root mean square deviation (RMSD), the mean error of the energies (ER), the standard deviation of the error (SDER) or the mean absolute error (AER), overestimate the distance between potentials. Moreover, their precise statistical meaning is far from clear. In this article, a new measure of the distance between potential energy functions is defined which overcomes the aforementioned difficulties. In addition, its precise physical meaning is discussed, the important issue of its additivity is investigated and some possible applications are proposed. Finally, two of these applications are illustrated with practical examples: the study of the van der Waals energy, as implemented in CHARMM, in the Trp-Cage protein (PDB code 1L2Y) and the comparison of different levels of the theory in the ab initio study of the Ramachandran map of the model peptide HCO-L-Ala-NH2.

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Comparison of generalized born and poisson models: Energetics and dynamics of HIV protease

Cited by 102 publications

References 50 publications

HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations

HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations

Peptide and Protein Folding and Conformational Equilibria: Theoretical Treatment of Electrostatics and Hydrogen Bonding with Implicit Solvent Models

A physically meaningful method for the comparison of potential energy functions

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