Effect of mutation at the interface of Trp-repressor dimeric protein: a steered molecular dynamics simulation.

The strength of key interfacial contacts that stabilize protein-protein interactions have been studied by computer simulation. Experimentally, changes in the interface are evaluated by generating specific mutations at one or more points of the protein structure. Here, such an evaluation is performed by means of steered molecular dynamics and use of a dimeric model of tryptophan repressor and in-silico mutants as a test case. Analysis of four particular cases shows that, in principle, it is possible to distinguish between wild-type and mutant forms by examination of the total energy and force-extension profiles. In particular, detailed atomic level structural analysis indicates that specific mutations at the interface of the dimeric model (positions 19 and 39) alter interactions that appear in the wild-type form of tryptophan repressor, reducing the energy and force required to separate both subunits.

On the role of short and strong hydrogen bonds on the mechanism of action of a model chymotrypsine active site.

The electronic properties of a chemical model that mimics the His-57...Asp-102 catalytic residues of alpha- chymotrypsine during the transition from normal hydrogen bond to short and strong hydrogen-bond regimes are presented. The results suggest that upon a global external stimulus induced by compression, the system response is the transfer of the nucleophilic reactivity from the model Asp-102 moiety toward the model His-57 fragment in the hydrogen-bonded complex. In this way, the catalytic effect may be consistently explained on the basis of a pair site reactivity model framed on the second-order static density response function.

Hydrogen bonds and heat diffusion in α-helices: a computational study.

Recent evidence has shown a correlation between the heat diffusion pathways and the known allosteric communication pathways in proteins. Allosteric communication in proteins is a central, yet unsolved, problem in biochemistry, and the study and characterization of the structural determinants that mediate energy transfer among different parts of proteins is of major importance. In this work, we characterized the role of hydrogen bonds in diffusivity of thermal energy for two sets of α-helices with different abilities to form hydrogen bonds. These hydrogen bonds can be a constitutive part of the α-helices or can arise from the lateral chains. In our in vacuo simulations, it was observed that α-helices with a higher possibility of forming hydrogen bonds also had higher rates of thermalization. Our simulations also revealed that heat readily flowed through atoms involved in hydrogen bonds. As a general conclusion, according to our simulations, hydrogen bonds fulfilled an important role in heat diffusion in structural patters of proteins.