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Gergely Tóth

Publications and source records attributed to Gergely Tóth.

7 recordsLinked to original sources
PubMed2006

Closing of the flaps of HIV-1 protease induced by substrate binding: a model of a flap closing mechanism in retroviral aspartic proteases.

The active site of aspartic proteases is covered by one or more flaps, which control access to the active site and play a significant role in the binding of the substrate. An extensive conformational change of the flaps takes place upon binding of substrate to the active site. A long molecular dynamics simulation was performed on the complex consisting of a peptide (CA-p2) from a natural substrate cleavage site of the gag/pol polyprotein placed in the active site of HIV-1 protease (PR) with an open flap conformation. During the simulation, the substrate induced the closing of the flaps into the closed conformation in an asymmetrical way through a hydrophobic intermediate state cluster. The nature of the residues of HIV-1 PR identified to be important in the flap closing mechanism is conserved across known structures of retroviral aspartic proteases family. The flap closing mechanism described in HIV-1 PR is proposed to be a general model for flap closing in retroviral aspartic proteases.

HIV Protease↗
PubMed2006

Structure of BRIJ-35 nonionic surfactant in water: a reverse Monte Carlo study.

There are some contradictions in the literature on the structure of micelles formed by the BRIJ-35 surfactant in water. One can find reasonable differences in the aggregation numbers and micellar sizes, but there is a lack of data on the intermicellar structure. In this study, we reevaluated the small-angle neutron scattering experiments performed previously on the BRIJ-35 surfactant in the concentration range of 5-200 g/dm3 at 20, 40, and 60 degrees C. The data were analyzed with a reverse Monte Carlo-type method developed recently for colloids. The micelles were modeled as spherical cores representing the hydrophobic parts and number of balls put on the cores to mimic the hydrated hydrophilic chains. The simulations provided data on the mean aggregation number and on the extent of hydration of the hydrophilic shell of the micelles. We obtained intermicellar pair-correlation functions indicating different micelle-micelle interactions from the usually assumed hard-sphere ones.

Journal Article↗
PubMed2005

Pair potentials from diffraction data on liquids: a neural network solution.

The inverse theorem of liquids states a one to one correspondence between classical mechanical pair potentials and structural functions. Molecular-dynamics and Monte Carlo simulations provide exact structural functions for known pair interactions. There is no exact or widespread method in the opposite direction, where the pair interactions are to be determined from a priori known pair-correlation functions or structure factors. The methods based on the integral equation theories of liquids are approximate and the iterative refinements of pair potentials with simulations take a long time. We applied artificial neural networks to get pair interactions from known structure factors in this study. We performed molecular-dynamics simulations on one-component systems with different pair potentials and the structure factors were calculated. To optimize (train) the weights of neural networks 2000 pair interaction-structure factor pairs were used. The performance of the method was tested on further 200 data pairs. The method provided reasonable potentials for the majority of the systems opening a "quick and dirty" method to determine pair interactions.

Journal Article↗
PubMed2005

Flap opening mechanism of HIV-1 protease.

The active site of aspartic proteases, such as HIV-1 protease (PR), is covered by one or more flaps, which restrict access to the active site. For HIV-1 PR, X-ray diffraction studies suggested that in the free enzyme the two flaps are packed onto each other loosely in a semi-open conformation, while molecular dynamics (MD) studies observed that the flaps can also separate into open conformations. In this study, the mechanism of flap opening and the structure and dynamics of HIV-1 PR with semi-open and open flap conformations were investigated using molecular dynamics simulations. The flaps showed complex dynamic behavior as two distinct mechanisms of flap opening and various stable flap conformations (semi-open, open and curled) were observed during the simulations. A network of weakly polar interactions between the flaps were proposed to be responsible for stabilizing the semi-open flap conformation. It is hypothesized that such interactions could be responsible for making flap opening a highly sensitive gating mechanism which control access to the active site.

Binding Sites↗
PubMed2004

Evaluation of small-angle x-ray scattering data of a Raney-type Ni catalyst with computer simulation.

A reverse Monte Carlo-type simulation method was developed for the evaluation of anomalous small-angle x-ray scattering data of a Raney-type Ni catalyst. Based on other experimental data the catalytic Ni particles were modeled as small crystalline cylinders dispersed in the matrix. The average size of the Ni particles and their pair-correlation function were determined. Despite the unknown density of the catalyst, it is shown that each particle has about 2 neighbors in the first neighboring shell independent of the modeling density, and the position of the first peak of the pair-correlation function does not depend on the modeling density. A method was elaborated to get reasonable performance of the Reverse Monte Carlo-type simulation. The scattered intensity was calculated on the basis of probe scattering atoms put inside the cylinders. The effects of the omission of the real number of the atoms, the unknown density, the lack of normalization and the uncertainties in the cross sections were unified in two constants that were determined during the simulation. The method can be used for nanoparticles with other shape, where analytic form factors are complicated, and it may be powerful in the investigation of the usually neglected or simplified inter-particle structure of these systems.

Journal Article↗
PubMed2003

Fast protein structure prediction using Monte Carlo simulations with modal moves.

Using normal modes to generate torsion space moves in Monte Carlo simulations of peptides and proteins is not a new idea; nevertheless, despite its power it has not received widespread application. We show that such a "Modal Monte Carlo" approach is an efficient tool for ab initio predictions of small-protein structures. We apply this method to the Trp cage, a 20-residue polypeptide designed to fold rapidly into a structure that includes tertiary contacts, despite its short length. We achieve a high-quality ab initio structure prediction in about 2 orders of magnitude less computation time than state of the art molecular dynamics techniques.

Computer Simulation↗