Shura Hayryan

SMMP) A modern package for simulation of proteins

Abstract A Fortran package is presented which provides useful routines for molecular simulation of proteins within the standard geometry model. Highly efficient algorithms for the calculation of energy and its derivatives are implemented. A set of energy minimization routines and modern Monte Carlo algorithms are added. Three different parameter sets are used to calculate the internal energy: ECEPP/2 potential, ECEPP/3 and the FLEX potential. The solvation energy of the protein can be calculated using the solvent accessible area method. The program is fast and may be successfully exploited even on a single PC. The code is free and open, and can be easily modified. Hence, the package allows researchers and students in a simple and inexpensive way to become familiar with protein simulation techniques, and is especially suitable for lecturers teaching molecular simulation. Yet, when exploited on advanced computers or PC clusters, it is a powerful tool and also valuable for advanced researchers.

An enhanced version of SMMP—open-source software package for simulation of proteins ✩

Abstract We describe a revised and updated version of the program package SMMP ( S imple M olecular M echanics for P roteins) [F. Eisenmenger, U.H.E. Hansmann, Sh. Hayryan, C.-K. Hu, Comput. Phys. Comm. 138 (2001) 192–212]. SMMP is an open-source FORTRAN package for molecular simulation of proteins within the standard geometry model. It is designed as a simple and inexpensive tool for researchers and students to become familiar with protein simulation techniques. This announcement describes the first major revision of this software package and its newly added features. Program summary Title of program: SMMP Catalogue identifier: ADOJ − v2 − 0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADOJ_v2_0 Program obtainable from: CPC Program Library, Queens University of Belfast, N. Ireland Operating system under which the program has been tested: LINUX system Programming language used: FORTRAN Computer: PC Pentium Number of lines in distributed program, including test data, etc.: 18 492 Number of bytes in distributed program, including test data, etc.: 278 995 Distribution format: ASCII Card punching code: ASCII Catalogue Identifier of previous version: ADOJ Journal Reference of previous version: F. Eisenmenger, U.H.E. Hansmann, Sh. Hayryan, C.-K. Hu, Comput. Phys. Comm. 138 (2001) 192–212 Does the new version supersede the previous version?: Yes Nature of physical problem: Molecular mechanics computations and Monte Carlo simulation of proteins Reasons for the new version: Increased functionality Summary of revisions: Changes in energy function and protein representation; differences in program structure and organization; new functionalities added; miscellaneous changes and additions Method of solution: Utilizes ECEPP2/3 and FLEX potentials. Includes Monte Carlo simulation algorithms for canonical, as well as for generalized ensembles Restrictions on the complexity of the problem: The consumed CPU time increases with the size of protein molecule Typical running time: Depends on the size of the molecule under simulation Unusual features of the program: No

A new analytical method for computing solvent-accessible surface area of macromolecules and its gradients

In the calculation of thermodynamic properties and three‐dimensional structures of macromolecules, such as proteins, it is important to have an efficient algorithm for computing the solvent‐accessible surface area of macromolecules. Here, we propose a new analytical method for this purpose. In the proposed algorithm we consider the transformation that maps the spherical circles formed by intersection of the atomic surfaces in three‐dimensional space onto the circles on a two‐dimensional plane, and the problem of computing the solvent‐accessible surface area is reduced to the problem of computing the corresponding curve integrals on the plane. This allows to consider only the integrals along the circular trajectories on the plane. The algorithm is suitable for parallelization. Testings on many proteins as well as the comparison to the other analogous algorithms have shown that our method is accurate and efficient.

ARVO: A Fortran package for computing the solvent accessible surface area and the excluded volume of overlapping spheres via analytic equations ✩

In calculating the solvation energy of proteins, the hydration effects, drug binding, molecular docking, etc., it is important to have an efficient and exact algorithms for computing the solvent accessible surface area and the excluded volume of macromolecules. Here we present a Fortran package based on the new exact analytical methods for computing volume and surface area of overlapping spheres. In the considered procedure the surface area and volume are expressed as surface integrals of the second kind over the closed region. Using the stereographic projection the surface integrals are transformed to a sum of double integrals which are reduced to the curve integrals. MPI Fortran version is described as well. The package is also useful for computing the percolation probability of continuum percolation models.

Folding of the Protein Domain hbSBD

The folding of the alpha-helix domain hbSBD of the mammalian mitochondrial branched-chain alpha-ketoacid dehydrogenase complex is studied by the circular dichroism technique in absence of urea. Thermal denaturation is used to evaluate various thermodynamic parameters defining the equilibrium unfolding, which is well described by the two-state model with the folding temperature T(F) = 317.8 +/- 1.95 K and the enthalpy change DeltaH(G) = 19.67 +/- 2.67 kcal/mol. The folding is also studied numerically using the off-lattice coarse-grained Go model and the Langevin dynamics. The obtained results, including the population of the native basin, the free-energy landscape as a function of the number of native contacts, and the folding kinetics, also suggest that the hbSBD domain is a two-state folder. These results are consistent with the biological function of hbSBD in branched-chain alpha-ketoacid dehydrogenase.

Microscopical approach to the helix–coil transition in DNA

A model Hamiltonian for double-strand polynucleotides is suggested to describe the phenomenon of helix–coil transition. The Hamiltonian is constructed using solely the microscopical, pure physical quantities, characterizing the molecular chain, namely the energy of hydrogen-bond formation and the number of conformations of repeated unit. Realistic constraints are imposed on the conformations of chain in the case of loop formation. The advantage of the suggested approach is that the parameters of the model can be obtained from independent calculations or experiments. It is shown that with the approximation of neglecting the effect of large loops, the model of DNA is reduced to the generalized microscopical model of polypeptide chain.

Efficient combination of Wang–Landau and transition matrix Monte Carlo methods for protein simulations

An efficient combination of the Wang‐Landau and transition matrix Monte Carlo methods for protein and peptide simulations is described. At the initial stage of simulation the algorithm behaves like the Wang‐Landau algorithm, allowing to sample the entire interval of energies, and at the later stages, it behaves like transition matrix Monte Carlo method and has significantly lower statistical errors. This combination allows to achieve fast convergence to the correct values of density of states. We propose that the violation of TTT identities may serve as a qualitative criterion to check the convergence of density of states. The simulation process can be parallelized by cutting the entire interval of simulation into subintervals. The violation of ergodicity in this case is discussed. We test the algorithm on a set of peptides of different lengths and observe good statistical convergent properties for the density of states. We believe that the method is of general nature and can be used for simulations of other systems with either discrete or continuous energy spectrum.

Multicanonical parallel simulations of proteins with continuous potentials

The determination of the three‐dimensional (3D) structure of a protein or peptide is a very important research problem in biological and medical sciences. Anfinsens experiments (Science 1973, 181, 223) on renaturation of denatured proteins have shown that the native 3D structure of a (small) protein at low (room) temperatures is uniquely determined by its amino acid sequence, which suggests that it might be possible to determine the 3D structure of a protein from its amino acid sequence by pure computations. As a step toward that goal, in this article we present a simple approach for parallelization of multicanonical Monte Carlo simulations of proteins with continuous potentials. Our method is based on the parallel calculation of the protein energy function. The algorithm is tested by simulated annealing and multicanonical simulations of two small peptides, and known results are reproduced accurately. An acceptable degree of parallelization can be achieved in the simulation of Protein L using up to 30 PCs.

Enveloping triangulation method for detecting internal cavities in proteins and algorithm for computing their surface areas and volumes

Detection and quantitative characterization of the internal cavities in proteins remain an important topic in studying protein structure and function. Here we propose a new analytical method for detecting the existence of cavities in proteins. The method is based on constructing the special enveloping triangulation enclosing the cavities. Based on this method, we develop an algorithm and a fortran package, CAVE, for computing volumes and surface areas of cavities in proteins. We first test our method and algorithm in some artificial systems of spheres and find that the calculated results are consistent with exact results. Then we apply the package to compute volumes and surface areas of cavities for some protein structures in the Protein Data Bank. We compare our calculated results with those obtained by some other methods and find that our approach is reliable.

CAVE: A package for detection and quantitative analysis of internal cavities in a system of overlapping balls: Application to proteins

We developed a software package (CAVE) in Fortran language to detect internal cavities in proteins which can be applied also to an arbitrary system of balls. The volume, the surface area and other quantitative characteristics of the cavities can be calculated. The code is based on the recently suggested enveloping triangulation algorithm [J. Busa et al., J. Comp. Chem. 30 (2009) 346] for computing volume and surface area of the cavity by analytical equations. Different standard sets of atomic radii can be used. The PDB compatible file containing the atomic coordinates must be stored on the disk in advance. Testing of the code on different proteins and artificial ball systems showed efficiency and accuracy of the algorithm. The program is fast. It can handle a system of several thousands of balls in the order of seconds on contemporary PCs. The code is open source and free.