9,730 research outputs found
The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds
We extend the effective fragment molecular orbital method (EFMO) into
treating fragments connected by covalent bonds. The accuracy of EFMO is
compared to FMO and conventional ab initio electronic structure methods for
polypeptides including proteins. Errors in energy for RHF and MP2 are within 2
kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides
similar to FMO but obtained two to five times faster. For proteins, the errors
are also within a few kcal/mol of the FMO results. We developed both the RHF
and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures
had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip
Ab-Initio Calculation of Molecular Aggregation Effects: a Coumarin-343 Case Study
We present time-dependent density functional theory (TDDFT) calculations for
single and dimerized Coumarin-343 molecules in order to investigate the quantum
mechanical effects of chromophore aggregation in extended systems designed to
function as a new generation of sensors and light-harvesting devices. Using the
single-chromophore results, we describe the construction of effective
Hamiltonians to predict the excitonic properties of aggregate systems. We
compare the electronic coupling properties predicted by such effective
Hamiltonians to those obtained from TDDFT calculations of dimers, and to the
coupling predicted by the transition density cube (TDC) method. We determine
the accuracy of the dipole-dipole approximation and TDC with respect to the
separation distance and orientation of the dimers. In particular, we
investigate the effects of including Coulomb coupling terms ignored in the
typical tight-binding effective Hamiltonian. We also examine effects of orbital
relaxation which cannot be captured by either of these models
Interface of the polarizable continuum model of solvation with semi-empirical methods in the GAMESS program
An interface between semi-empirical methods and the polarized continuum model
(PCM) of solvation successfully implemented into GAMESS following the approach
by Chudinov et al (Chem. Phys. 1992, 160, 41). The interface includes energy
gradients and is parallelized. For large molecules such as ubiquitin a
reasonable speedup (up to a factor of six) is observed for up to 16 cores. The
SCF convergence is greatly improved by PCM for proteins compared to the gas
phase
Polarizable molecular interactions in condensed phase and their equivalent nonpolarizable models
Earlier, using phenomenological approach, we showed that in some cases
polarizable models of condensed phase systems can be reduced to nonpolarizable
equivalent models with scaled charges. Examples of such systems include ionic
liquids, TIPnP-type models of water, protein force fields, and others, where
interactions and dynamics of inherently polarizable species can be accurately
described by nonpolarizable models. To describe electrostatic interactions, the
effective charges of simple ionic liquids are obtained by scaling the actual
charges of ions by a factor of 1/sqrt(eps_el), which is due to electronic
polarization screening effect; the scaling factor of neutral species is more
complicated. Here, using several theoretical models, we examine how exactly the
scaling factors appear in theory, and how, and under what conditions,
polarizable Hamiltonians are reduced to nonpolarizable ones. These models allow
one to trace the origin of the scaling factors, determine their values, and
obtain important insights on the nature of polarizable interactions in
condensed matter systems.Comment: 43 pages, 3 figure
Computational structure‐based drug design: Predicting target flexibility
The role of molecular modeling in drug design has experienced a significant revamp in the last decade. The increase in computational resources and molecular models, along with software developments, is finally introducing a competitive advantage in early phases of drug discovery. Medium and small companies with strong focus on computational chemistry are being created, some of them having introduced important leads in drug design pipelines. An important source for this success is the extraordinary development of faster and more efficient techniques for describing flexibility in three‐dimensional structural molecular modeling. At different levels, from docking techniques to atomistic molecular dynamics, conformational sampling between receptor and drug results in improved predictions, such as screening enrichment, discovery of transient cavities, etc. In this review article we perform an extensive analysis of these modeling techniques, dividing them into high and low throughput, and emphasizing in their application to drug design studies. We finalize the review with a section describing our Monte Carlo method, PELE, recently highlighted as an outstanding advance in an international blind competition and industrial benchmarks.We acknowledge the BSC-CRG-IRB Joint Research Program in Computational Biology. This work was supported by a grant
from the Spanish Government CTQ2016-79138-R.J.I. acknowledges support from SVP-2014-068797, awarded by the Spanish Government.Peer ReviewedPostprint (author's final draft
Molecular theory of solvation: Methodology summary and illustrations
Integral equation theory of molecular liquids based on statistical mechanics
is quite promising as an essential part of multiscale methodology for chemical
and biomolecular nanosystems in solution. Beginning with a molecular
interaction potential force field, it uses diagrammatic analysis of the
solvation free energy to derive integral equations for correlation functions
between molecules in solution in the statistical-mechanical ensemble. The
infinite chain of coupled integral equations for many-body correlation
functions is reduced to a tractable form for 2- or 3-body correlations by
applying the so-called closure relations. Solving these equations produces the
solvation structure with accuracy comparable to molecular simulations that have
converged but has a critical advantage of readily treating the effects and
processes spanning over a large space and slow time scales, by far not feasible
for explicit solvent molecular simulations. One of the versions of this
formalism, the three-dimensional reference interaction site model (3D-RISM)
integral equation complemented with the Kovalenko-Hirata (KH) closure
approximation, yields the solvation structure in terms of 3D maps of
correlation functions, including density distributions, of solvent interaction
sites around a solute (supra)molecule with full consistent account for the
effects of chemical functionalities of all species in the solution. The
solvation free energy and the subsequent thermodynamics are then obtained at
once as a simple integral of the 3D correlation functions by performing
thermodynamic integration analytically.Comment: 24 pages, 10 figures, Revie
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