TeraChem: Accelerating electronic structure and ab initio molecular dynamics with graphical processing units.

Developed over the past decade, TeraChem is an electronic structure and ab initio molecular dynamics software package designed from the ground up to leverage graphics processing units (GPUs) to perform large-scale ground and excited state quantum chemistry calculations in the gas and the condensed phase. TeraChem's speed stems from the reformulation of conventional electronic structure theories in terms of a set of individually optimized high-performance electronic structure operations (e.g.

Solving the structure of Lgl2, a difficult blind test of unsupervised structure determination.

In the companion paper by Ufimtsev and Levitt [Ufimtsev IS, Levitt M (2019) , 10.1073/pnas.1821512116], we presented a method for unsupervised solution of protein crystal structures and demonstrated its utility by solving several test cases of known structure in the 2.

Unsupervised determination of protein crystal structures.

We present a method for automatic solution of protein crystal structures. The method proceeds with a single initial model obtained, for instance, by molecular replacement (MR). If a good-quality search model is not available, as often is the case with MR of distant homologs, our method first can automatically screen a large pool of poorly placed models and single out promising candidates for further processing if there are any.

Structural insights into the aPKC regulatory switch mechanism of the human cell polarity protein lethal giant larvae 2.

Metazoan cell polarity is controlled by a set of highly conserved proteins. Lethal giant larvae (Lgl) functions in apical-basal polarity through phosphorylation-dependent interactions with several other proteins as well as the plasma membrane. Phosphorylation of Lgl by atypical protein kinase C (aPKC), a component of the partitioning-defective (Par) complex in epithelial cells, excludes Lgl from the apical membrane, a crucial step in the establishment of epithelial cell polarity.

Analytic first derivatives of floating occupation molecular orbital-complete active space configuration interaction on graphical processing units.

The floating occupation molecular orbital-complete active space configuration interaction (FOMO-CASCI) method is a promising alternative to the state-averaged complete active space self-consistent field (SA-CASSCF) method. We have formulated the analytic first derivative of FOMO-CASCI in a manner that is well-suited for a highly efficient implementation using graphical processing units (GPUs). Using this implementation, we demonstrate that FOMO-CASCI gradients are of similar computational expense to configuration interaction singles (CIS) or time-dependent density functional theory (TDDFT).

An atomic orbital-based formulation of the complete active space self-consistent field method on graphical processing units.

Despite its importance, state-of-the-art algorithms for performing complete active space self-consistent field (CASSCF) computations have lagged far behind those for single reference methods. We develop an algorithm for the CASSCF orbital optimization that uses sparsity in the atomic orbital (AO) basis set to increase the applicability of CASSCF. Our implementation of this algorithm uses graphical processing units (GPUs) and has allowed us to perform CASSCF computations on molecular systems containing more than one thousand atoms.

Generating Efficient Quantum Chemistry Codes for Novel Architectures.

We describe an extension of our graphics processing unit (GPU) electronic structure program TeraChem to include atom-centered Gaussian basis sets with d angular momentum functions. This was made possible by a "meta-programming" strategy that leverages computer algebra systems for the derivation of equations and their transformation to correct code. We generate a multitude of code fragments that are formally mathematically equivalent, but differ in their memory and floating-point operation footprints.

Ab initio quantum chemistry for protein structures.

Structural properties of over 55 small proteins have been determined using both density-based and wave-function-based electronic structure methods in order to assess the ability of ab initio "force fields" to retain the properties described by experimental structures measured with crystallography or nuclear magnetic resonance. The efficiency of the GPU-based quantum chemistry algorithms implemented in our TeraChem program enables us to carry out systematic optimization of ab initio protein structures, which we compare against experimental and molecular mechanics force field references. We show that the quality of the ab initio optimized structures, as judged by conventional protein health metrics, increases with increasing basis set size.

Excited-State Electronic Structure with Configuration Interaction Singles and Tamm-Dancoff Time-Dependent Density Functional Theory on Graphical Processing Units.

Excited-state calculations are implemented in a development version of the GPU-based TeraChem software package using the configuration interaction singles (CIS) and adiabatic linear response Tamm-Dancoff time-dependent density functional theory (TDA-TDDFT) methods. The speedup of the CIS and TDDFT methods using GPU-based electron repulsion integrals and density functional quadrature integration allows full ab initio excited-state calculations on molecules of unprecedented size. CIS/6-31G and TD-BLYP/6-31G benchmark timings are presented for a range of systems, including four generations of oligothiophene dendrimers, photoactive yellow protein (PYP), and the PYP chromophore solvated with 900 quantum mechanical water molecules.

Dynamic Precision for Electron Repulsion Integral Evaluation on Graphical Processing Units (GPUs).

It has recently been demonstrated that novel streaming architectures found in consumer video gaming hardware such as graphical processing units (GPUs) are well-suited to a broad range of computations including electronic structure theory (quantum chemistry). Although recent GPUs have developed robust support for double precision arithmetic, they continue to provide 2-8× more hardware units for single precision. In order to maximize performance on GPU architectures, we present a technique of dynamically selecting double or single precision evaluation for electron repulsion integrals (ERIs) in Hartree-Fock and density functional self-consistent field (SCF) calculations.

GPU-accelerated molecular modeling coming of age.

Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling.

A multistate empirical valence bond model for solvation and transport simulations of OH- in aqueous solutions.

We describe a new multistate empirical valence bond (MS-EVB) model of OH(-) in aqueous solutions. This model is based on the recently proposed "charged ring" parameterization for the intermolecular interaction of hydroxyl ion with water [Ufimtsev, et al., Chem.

Quantum Chemistry on Graphical Processing Units. 3. Analytical Energy Gradients, Geometry Optimization, and First Principles Molecular Dynamics.

We demonstrate that a video gaming machine containing two consumer graphical cards can outpace a state-of-the-art quad-core processor workstation by a factor of more than 180× in Hartree-Fock energy + gradient calculations. Such performance makes it possible to run large scale Hartree-Fock and Density Functional Theory calculations, which typically require hundreds of traditional processor cores, on a single workstation. Benchmark Born-Oppenheimer molecular dynamics simulations are performed on two molecular systems using the 3-21G basis set - a hydronium ion solvated by 30 waters (94 atoms, 405 basis functions) and an aspartic acid molecule solvated by 147 waters (457 atoms, 2014 basis functions).

Observation of a Zundel-like transition state during proton transfer in aqueous hydroxide solutions.

It is generally accepted that the anomalous diffusion of the aqueous hydroxide ion results from its ability to accept a proton from a neighboring water molecule; yet, many questions exist concerning the mechanism for this process. What is the solvation structure of the hydroxide ion? In what way do water hydrogen bond dynamics influence the transfer of a proton to the ion? We present the results of femtosecond pump-probe and 2D infrared experiments that probe the O-H stretching vibration of a solution of dilute HOD dissolved in NaOD/D(2)O. Upon the addition of NaOD, measured pump-probe transients and 2D IR spectra show a new feature that decays with a 110-fs time scale.

Quantum Chemistry on Graphical Processing Units. 2. Direct Self-Consistent-Field Implementation.

We demonstrate the use of graphical processing units (GPUs) to carry out complete self-consistent-field calculations for molecules with as many as 453 atoms (2131 basis functions). Speedups ranging from 28× to 650× are achieved as compared to a mature third-party quantum chemistry program (GAMESS) running on a traditional CPU. The computational organization used to construct the Coulomb and exchange operators is discussed.

Quantum Chemistry on Graphical Processing Units. 1. Strategies for Two-Electron Integral Evaluation.

Modern videogames place increasing demands on the computational and graphical hardware, leading to novel architectures that have great potential in the context of high performance computing and molecular simulation. We demonstrate that Graphical Processing Units (GPUs) can be used very efficiently to calculate two-electron repulsion integrals over Gaussian basis functions [Formula: see text] the first step in most quantum chemistry calculations. A benchmark test performed for the evaluation of approximately 10(6) (ss|ss) integrals over contracted s-orbitals showed that a naïve algorithm implemented on the GPU achieves up to 130-fold speedup over a traditional CPU implementation on an AMD Opteron.