On the Temperature and Pressure Dependence of a Range of Properties of a Type of Water Model Commonly Used in High-Temperature Protein Unfolding Simulations

Walser, Regula; Mark, Alan E.; Gunsteren, Wilfred F. van

doi:10.1016/s0006-3495(00)76820-2

Cited by 46 publications

(36 citation statements)

References 37 publications

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“…These trends are consistent with our earlier work 19 and findings from other groups. 21,22 Further details regarding the behavior of our water model and detailed solvation properties of peptides and proteins have been presented by Beck et al 23 Overall our pure water simulations are in agreement with the available experimental results across a variety of temperatures, suggesting that this water model does not introduce artifacts when used in hightemperature protein denaturation studies.…”

Section: Resultssupporting

confidence: 78%

Increasing Temperature Accelerates Protein Unfolding Without Changing the Pathway of Unfolding

Day

Bennion

Ham

et al. 2002

Journal of Molecular Biology

325

264

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We have traditionally relied on extremely elevated temperatures (498 K, 225 8C) to investigate the unfolding process of proteins within the timescale available to molecular dynamics simulations with explicit solvent. However, recent advances in computer hardware have allowed us to extend our thermal denaturation studies to much lower temperatures. Here we describe the results of simulations of chymotrypsin inhibitor 2 at seven temperatures, ranging from 298 K to 498 K. The simulation lengths vary from 94 ns to 20 ns, for a total simulation time of 344 ns, or 0.34 ms. At 298 K, the protein is very stable over the full 50 ns simulation. At 348 K, corresponding to the experimentally observed melting temperature of CI2, the protein unfolds over the first 25 ns, explores partially unfolded conformations for 20 ns, and then refolds over the last 35 ns. Above its melting temperature, complete thermal denaturation occurs in an activated process. Early unfolding is characterized by sliding or breathing motions in the protein core, leading to an unfolding transition state with a weakened core and some loss of secondary structure. After the unfolding transition, the core contacts are rapidly lost as the protein passes on to the fully denatured ensemble. While the overall character and order of events in the unfolding process are well conserved across temperatures, there are substantial differences in the timescales over which these events take place. We conclude that 498 K simulations are suitable for elucidating the details of protein unfolding at a minimum of computational expense.

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Section: Resultssupporting

confidence: 78%

Increasing Temperature Accelerates Protein Unfolding Without Changing the Pathway of Unfolding

Day

Bennion

Ham

et al. 2002

Journal of Molecular Biology

325

264

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“…The force field parameters are normally fit at RT, and it is not surprising that the resulting potential function cannot reproduce some properties at higher temperatures well. The SPC water model may also contribute to the errors in our simulation because, as pointed out recently by van Gusteren and coworkers, the properties of SPC water, such as the thermal expansion coefficient, heat capacity, and diffusion constants deviate significantly from experiments at higher temperatures (24). The same is probably true for the TIP3P water as used in Garcia and Sanbonmatsu's simulation.…”

Section: Resultsmentioning

confidence: 72%

The free energy landscape for β hairpin folding in explicit water

Zhou

Berne

Germain

2001

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

510

595

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The folding free energy landscape of the C-terminal ␤ hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and OPLSAA force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME͞RESPA. The simulation results show that the hydrophobic core and the ␤ strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The ␤ hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.U nderstanding protein folding is one of the most challenging problems remaining in molecular biology (1-5). Recent advances in experimental techniques that probe proteins at different stages during the folding process have shed light on the nature of the physical mechanisms and relevant interactions that determine the kinetics of folding, binding, function, and thermodynamic stability (2-5). However, many of the details of protein folding pathways remain unknown. Computer simulations performed at various levels of complexity ranging from simple lattice models, models with continuum solvent, to all atom models with explicit solvent can be used to supplement experiment and fill in some of the gaps in our knowledge about folding pathways. Much of today's theoretical understanding has been tested in minimalist lattice or off-lattice models. All-atom simulations of protein unfolding at high temperatures have also revealed many important features about the protein folding process, even though they are limited by the fact that the free energy landscape explored at high temperature might be very different from the landscape at biological temperatures. Allatom protein folding in explicit solvent still remains a challenge in computational biology.The free energy landscape of native proteins in explicit solvent is believed to be partially rugged and funnel-like (6) because of the energy barriers caused by van der Waals repulsions and torsional energy barriers. At room temperature (RT), protein systems get trapped in many local minima. This trapping limits the capacity to effectively sample configurational space. Many methods have been proposed to enhance the conformation space sampling (7). In this work, we use the replica exchange or parallel tempering method (8) to increase barrier crossing events.As one of the smallest naturally occurring systems, which exhibits many features of a full size protein and also is a faster folder (it folds in 6 s), the C-terminal ␤ hairpin of protein G has received much attention recently on bo...

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“…2000; Tarek & Tobias 2000Teeter et al 2001;Caliskan et al 2002;Paciaroni et al 2002). Highly viscous solvents, such as trehalose, suppress dynamical transition behaviour (Hagen et al 1995;Cordone et al 1999;Walser et al 2000), and neutron-scattering experiments on enzymes in a range of cryosolvents showed that the dynamical transition behaviour of the protein solution resembles that of the pure solvent (Bizzarri et al 2000;Reat et al 2000;Daniel et al 2003).…”

Section: Solvent Role In the Protein-glass Transitionmentioning

confidence: 99%

Structure, dynamics and reactions of protein hydration water

Smith

Merzel

Bondar

et al. 2004

Phil. Trans. R. Soc. Lond. B

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The apparent simplicity of the water molecule belies the wide range of fascinating protein phenomena in which it participates. We review recent computer simulation work on buried, internal water molecules, discussing the thermodynamics of water molecule binding and the participation of water in proton transfer reactions. Surface water molecules are also considered, with emphasis on the modification of average solvent structure on a protein surface, the role of water in the protein dynamical 'glass' transition and a simplified description of the protein motions thereby activated.

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On the Temperature and Pressure Dependence of a Range of Properties of a Type of Water Model Commonly Used in High-Temperature Protein Unfolding Simulations

Cited by 46 publications

References 37 publications

Increasing Temperature Accelerates Protein Unfolding Without Changing the Pathway of Unfolding

Increasing Temperature Accelerates Protein Unfolding Without Changing the Pathway of Unfolding

The free energy landscape for β hairpin folding in explicit water

Structure, dynamics and reactions of protein hydration water

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