Improvements to the APBS biomolecular solvation software suite

The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that has provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this manuscript, we discuss the models and capabilities that have recently been implemented within the APBS software package including: a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory based algorithm for determining p$K_a$ values, and an improved web-based visualization tool for viewing electrostatics

Accurate biomolecular simulations account for electronic polarization

International audienceIn this perspective, we discuss where and how accounting for electronic many-body polarization affects the accuracy of classical molecular dynamics simulations of biomolecules.While the effects of electronic polarization are highly pronounced for molecules with an opposite total charge, they are also non-negligible for interactions with overall neutral molecules. For instance, neglecting these effects in important biomolecules like amino acids and phospholipids affects the structure of proteins and membranes having a large impact on interpreting experimental data as well as building coarse grained models. With the combined advances in theory, algorithms and computational power it is currently realistic to perform simulations with explicit polarizable dipoles on systems with relevant sizes and complexity. Alternatively, the effects of electronic polarization can also be included at zero additional computational cost compared to standard fixed-charge force fields using the electronic continuum correction, as was recently demonstrated for several classes of biomolecules

Efficient minimization of multipole electrostatic potentials in torsion space

The development of models of macromolecular electrostatics capable of delivering improved fidelity to quantum mechanical calculations is an active field of research in computational chemistry. Most molecular force field development takes place in the context of models with full Cartesian coordinate degrees of freedom. Nevertheless, a number of macromolecular modeling programs use a reduced set of conformational variables limited to rotatable bonds. Efficient algorithms for minimizing the energies of macromolecular systems with torsional degrees of freedom have been developed with the assumption that all atom-atom interaction potentials are isotropic. We describe novel modifications to address the anisotropy of higher order multipole terms while retaining the efficiency of these approaches. In addition, we present a treatment for obtaining derivatives of atom-centered tensors with respect to torsional degrees of freedom. We apply these results to enable minimization of the Amoeba multipole electrostatics potential in a system with torsional degrees of freedom, and validate the correctness of the gradients by comparison to finite difference approximations. In the interest of enabling a complete model of electrostatics with implicit treatment of solvent-mediated effects, we also derive expressions for the derivative of solvent accessible surface area with respect to torsional degrees of freedom

Accurate Evaluation of Charge Asymmetry in Aqueous Solvation

Charge hydration asymmetry (CHA)--a characteristic dependence of hydration free energy on the sign of the solute charge--quantifies the asymmetric response of water to electric field at microscopic level. Accurate estimates of CHA are critical for understanding hydration effects ubiquitous in chemistry and biology. However, measuring hydration energies of charged species is fraught with significant difficulties, which lead to unacceptably large (up to 300%) variation in the available estimates of the CHA effect. We circumvent these difficulties by developing a framework which allows us to extract and accurately estimate the intrinsic propensity of water to exhibit CHA from accurate experimental hydration free energies of neutral polar molecules. Specifically, from a set of 504 small molecules we identify two pairs that are analogous, with respect to CHA, to the K+/F- pair--a classical probe for the effect. We use these "CHA-conjugate" molecule pairs to quantify the intrinsic charge-asymmetric response of water to the microscopic charge perturbations: the asymmetry of the response is strong, ~50% of the average hydration free energy of these molecules. The ability of widely used classical water models to predict hydration energies of small molecules correlates with their ability to predict CHA

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

IMAGE CHARGE SOLVATION MODEL (ICSM) FOR SIMULATING BIOMOLECULES AND KCSA ION-CHANNELS

We present an order N method for calculating electrostatic interactions that has been integrated into the molecular dynamics portion of the TINKER Molecular Modeling package. This method, termed the Image-Charge Solvation Model (ICSM), and introduced previously by Dr. Lin et al. (1) in 2009, is a hybrid electrostatic approach that combines the strengths of both explicit and implicit representations of the solvent. In this model, a multiple-image method is used to calculate reaction fields due to the implicit solvent while the Fast Multipole Method (FMM) is used to calculate the Coulomb interactions for all charges, including the charges in the explicit solvent part. The integrated package is validated through simulations of liquid water. The results are compared with those obtained by the Particle Mesh Ewald (PME) method that is built in the TINKER package. Timing performance of TINKER with the integrated ICSM is benchmarked on bulk water as a function of the size of the system. In particular, timing analysis results show that the ICSM outperforms the PME for sufficiently large systems with the break-even point at around 30,000 particles in the simulated system. To demonstrate the capability of the package on large macromolecules, the model is used to simulate the potassium channel KcsA