ResearchPad - theoretical-methods-and-algorithms https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[TURBOMOLE: Modular program suite for <i>ab initio</i> quantum-chemical and condensed-matter simulations]]> https://www.researchpad.co/article/elastic_article_13895 TURBOMOLE is a collaborative, multi-national software development project aiming to provide highly efficient and stable computational tools for quantum chemical simulations of molecules, clusters, periodic systems, and solutions. The TURBOMOLE software suite is optimized for widely available, inexpensive, and resource-efficient hardware such as multi-core workstations and small computer clusters. TURBOMOLE specializes in electronic structure methods with outstanding accuracy–cost ratio, such as density functional theory including local hybrids and the random phase approximation (RPA), GW-Bethe–Salpeter methods, second-order Møller–Plesset theory, and explicitly correlated coupled-cluster methods. TURBOMOLE is based on Gaussian basis sets and has been pivotal for the development of many fast and low-scaling algorithms in the past three decades, such as integral-direct methods, fast multipole methods, the resolution-of-the-identity approximation, imaginary frequency integration, Laplace transform, and pair natural orbital methods. This review focuses on recent additions to TURBOMOLE’s functionality, including excited-state methods, RPA and Green’s function methods, relativistic approaches, high-order molecular properties, solvation effects, and periodic systems. A variety of illustrative applications along with accuracy and timing data are discussed. Moreover, available interfaces to users as well as other software are summarized. TURBOMOLE’s current licensing, distribution, and support model are discussed, and an overview of TURBOMOLE’s development workflow is provided. Challenges such as communication and outreach, software infrastructure, and funding are highlighted.

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<![CDATA[An efficient strategy to estimate thermodynamics and kinetics of G protein-coupled receptor activation using metadynamics and maximum caliber]]> https://www.researchpad.co/article/5c3d830bd5eed0c48450c5d1

Computational strategies aimed at unveiling the thermodynamic and kinetic properties of G Protein-Coupled Receptor (GPCR) activation require extensive molecular dynamics simulations of the receptor embedded in an explicit lipid-water environment. A possible method for efficiently sampling the conformational space of such a complex system is metadynamics (MetaD) with path collective variables (CVs). Here, we applied well-tempered MetaD with path CVs to one of the few GPCRs for which both inactive and fully active experimental structures are available, the μ-opioid receptor (MOR), and assessed the ability of this enhanced sampling method to estimate the thermodynamic properties of receptor activation in line with those obtained by more computationally expensive adaptive sampling protocols. While n-body information theory analysis of these simulations confirmed that MetaD can efficiently characterize ligand-induced allosteric communication across the receptor, standard MetaD cannot be used directly to derive kinetic rates because transitions are accelerated by a bias potential. Applying the principle of Maximum Caliber (MaxCal) to the free-energy landscape of morphine-bound MOR reconstructed from MetaD, we obtained Markov state models that yield kinetic rates of MOR activation in agreement with those obtained by adaptive sampling. Taken together, these results suggest that the MetaD-MaxCal combination creates an efficient strategy for estimating the thermodynamic and kinetic properties of GPCR activation at an affordable computational cost.

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