Piero Procacci

ORAC: A Molecular dynamics program to simulate complex molecular systems with realistic electrostatic interactions

In this study, we present a new molecular dynamics program for simulation of complex molecular systems. The program, named ORAC, combines state‐of‐the‐art molecular dynamics (MD) algorithms with flexibility in handling different types and sizes of molecules. ORAC is intended for simulations of molecular systems and is specifically designed to treat biomolecules efficiently and effectively in solution or in a crystalline environment. Among its unique features are: (i) implementation of reversible and symplectic multiple time step algorithms (or r‐RESPA, reversible reference system propagation algorithm) specifically designed and tuned for biological systems with periodic boundary conditions; (ii) availability for simulations with multiple or single time steps of standard Ewald or smooth particle mesh Ewald (SPME) for computation of electrostatic interactions; and (iii) possibility of simulating molecular systems in a variety of thermodynamic ensembles. We believe that the combination of these algorithms makes ORAC more advanced than other MD programs using standard simulation algorithms. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1848–1862, 1997

A transferable polarizable electrostatic force field for molecular mechanics based on the chemical potential equalization principle

A polarizable electrostatic potential model for classical molecular mechanics is presented. Based on the chemical potential equalization (CPE) principle, the model is developed starting from the original formulation of Mortier, Ghosh, and Shankar [J. Am. Chem. Soc. 108, 4315 (1986)]. Following York and Yang [J. Chem. Phys. 104, 159 (1996)] we present an SP-basis CPE parametrization to describe realistically any sort of molecular system. By fitting ab initio electronic properties, such as dipole moment, polarizability and global molecular hardness of a restricted set of organic molecules, we derive atomic parameters to be applied to a more vast target set of compounds. We show, indeed, that the atomic CPE parameters calculated for the learning set of molecules give reliable values for several electronic properties of various compounds not included in the learning set. The multipole moments obtained by using the proposed CPE parametrization are compared to the results of a fixed charge parametrization like ...

Electrical response in chemical potential equalization schemes

In this paper we compare the polarization response given by two different chemical potential equalization schemes to be applied to molecular dynamics simulations: the standard fluctuating point charge model (FQ) and the atom–atom charge transfer model (AACT). We have tested the transferability of FQ and AACT parameters, fitted to the polarizability of small size alkanes and polyenes, to large size homologues. We show that the FQ scheme is not adequate for the n-alkanes as it strongly overestimates the polarizability tensor components as the number of carbon atoms increases. The FQ approach has been found more predictive for highly conjugated systems like polyenes, although still unsatisfactory. The AACT parameters tuned on ethane are instead perfectly transferable to alkanes of any length and conformation. The AACT scheme satisfactorily reproduces the polarization response also for highly conjugated systems.

COORDINATES SCALING AND MULTIPLE TIME STEP ALGORITHMS FOR SIMULATION OF SOLVATED PROTEINS IN THE NPT ENSEMBLE

Constant pressure and temperature algorithms have been derived based on a reversible multiple time step (r-RESPA) approach and a new modification of the particle mesh Ewald method. As such they provide very fast and accurate tools for simulation of complex molecular systems in ensembles other than the microcanonical. We have also developed a novel scaling scheme named atomic group scaling which is similar to atomic scaling, but has important computational advantages when used in conjunction with bond constraints. The investigation of the molecular and atomic group scaling schemes against static and dynamic properties of a test system (a solvated bovine pancreatic trypsin inhibitor) has confirmed their equivalence also for large molecules such as proteins. For the specific test system the simulation box cell volume upon changes of pressure decays to its equilibrium value within 5 ps of simulation for both approaches. This goes against theoretical arguments that molecular scaling would not be suitable for s...

TAMING THE EWALD SUM IN MOLECULAR DYNAMICS SIMULATIONS OF SOLVATED PROTEINS VIA A MULTIPLE TIME STEP ALGORITHM

Long range electrostatic forces are involved at a fundamental level in many biological phenomena. Their prohibitive computational costs often prevents their correct calculation in molecular dynamics (MD) simulations of biological molecules. In this paper we present a method to handle efficiently and exactly electrostatic interactions in MD simulations with periodic boundary conditions. Our scheme employs a multiple time step r‐RESPA integration algorithm in combination with the Ewald summation technique, and is specifically targeted to simulation of large size complex molecular systems such as solvated proteins. In this approach, the force associated with each particle of the system is partitioned into four components which evolve in time with distinct and increasingly longer time scales. We found that a suitable time scale separation is achieved by subdividing the direct space nonbonded interactions, inclusive of Coulombic and van der Waals contributions, in a short, medium and long range shells.The fast...

Glycerol condensed phases Part II.A molecular dynamics study of the conformational structure and hydrogen bonding

An analysis of the conformational properties and hydrogen bonding in the condensed phases of glycerol is reported using the same model as adopted in Part I (Phys. Chem. Chem. Phys., 1999, 1, 871). Structural properties of the liquid and glassy states are analyzed in relation to the molecular backbone conformation of the glycerol molecule. The effects of hydrogen bonding and of temperature on the conformational distribution are analyzed. The structural and dynamical properties of hydrogen bonding in glycerol are also investigated. The results are consistent with available experimental observations and clarify many important and interrelated aspects of the microscopic structure of liquid, glassy and crystalline phases of glycerol.

The nature of intermolecular interactions between aromatic amino acid residues

The nature of intermolecular interactions between aromatic amino acid residues has been investigated by a combination of molecular dynamics and ab initio methods. The potential energy surface of various interacting pairs, including tryptophan, phenilalanine, and tyrosine, was scanned for determining all the relevant local minima by a combined molecular dynamics and conjugate gradient methodology with the AMBER force field. For each of these minima, single‐point correlated ab initio calculations of the binding energy were performed. The agreement between empirical force field and ab initio binding energies of the minimum energy structures is excellent. Aromatic–aromatic interactions can be rationalized on the basis of electrostatic and van der Waals interactions, whereas charge transfer or polarization phenomena are small for all intermolecular complexes and, particularly, for stacked structures. Proteins 2002;48:117–125.

Calculation of optical spectra in liquid methanol using molecular dynamics and the chemical potential equalization method

We apply the chemical potential equalization (CPE) method to the calculation of the optical spectra in liquid methanol at 298 K and normal pressure. The configurations of the liquid are obtained by conventional molecular dynamics (MD) using a completely flexible all-atoms model. The infrared and Raman spectra are computed a posteriori using a CPE parametrization of methanol calibrated to reproduce the electronic properties of the isolated molecule evaluated with accurate ab initio calculations. The MD/CPE method reproduces correctly the optical spectra in the region of the intermolecular motions. The spectra are discussed and interpreted on the basis of hydrogen bonding structure and dynamics.

ORAC: A molecular dynamics simulation program to explore free energy surfaces in biomolecular systems at the atomistic level

We present the new release of the ORAC engine (Procacci et al., Comput Chem 1997, 18, 1834), a FORTRAN suite to simulate complex biosystems at the atomistic level. The previous release of the ORAC code included multiple time steps integration, smooth particle mesh Ewald method, constant pressure and constant temperature simulations. The present release has been supplemented with the most advanced techniques for enhanced sampling in atomistic systems including replica exchange with solute tempering, metadynamics and steered molecular dynamics. All these computational technologies have been implemented for parallel architectures using the standard MPI communication protocol. ORAC is an open‐source program distributed free of charge under the GNU general public license (GPL) at http://www.chim.unifi.it/orac.

An ab initio force field for the cofactors of bacterial photosynthesis

This article presents a new ab initio force field for the cofactors of bacterial photosynthesis, namely quinones and bacteriochlorophylls. The parameters has been designed to be suitable for molecular dynamics simulations of photosynthetic proteins by being compatible with the AMBER force field. To our knowledge, this is the first force field for photosynthetic cofactors based on a reliable set of ab initio density functional reference data for methyl bacteriochlorophyll a, methyl bacteriopheophytin a, and of a derivative of ubiquinone. Indeed, the new molecular mechanics force field is able to reproduce very well not only the experimental and ab initio structural properties and the vibrational spectra of the molecules, but also the eigenvectors of the molecular normal modes. For this reason it might also be helpful to understand vibrational spectroscopy results obtained on reaction center proteins.