Search results for "QM"
showing 10 items of 284 documents
Transition structure selectivity in enzyme catalysis: a QM/MM study of chorismate mutase
2001
Two different transition structures (TSs) have been located and characterized for the chorismate conversion to prephenate in Bacillus subtilis chorismate mutase by means of hybrid quantum-mechanical/molecular-mechanical (QM/MM) calculations. GRACE software, combined with an AM1/CHARMM24/TIP3P potential, has been used involving full gradient relaxation of the position of ca. 3300 atoms. These TSs have been connected with their respective reactants and products by the intrinsic reaction coordinate (IRC) procedure carried out in the presence of the protein environment, thus obtaining for the first time a realistic enzymatic reaction path for this reaction. Similar QM/MM computational schemes h…
Hybrid Schemes Based on Quantum Mechanics/Molecular Mechanics Simulations
2011
The development of characterization techniques, advanced synthesis methods, as well as molecular modeling has transformed the study of systems in a well-established research field. The current research challenges in biocatalysis and biotransformation evolve around enzyme discovery, design, and optimization. How can we find or create enzymes that catalyze important synthetic reactions, even reactions that may not exist in nature? What is the source of enzyme catalytic power? To answer these and other related questions, the standard strategies have evolved from trial-and-error methodologies based on chemical knowledge, accumulated experience, and common sense into a clearly multidisciplinary …
Binding and Reactivity of a Nitrile Oral Inhibitor of SARS-CoV-2 Main Protease Revealed by Computational Simulations
2021
We present a detailed analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against SARS-CoV-2 3CL protease. Classical and QM/MM Molecular Dynamics simulations are used to quantify the contributions to the binding free energy and the reaction mechanism for covalent inhibition. The small size of the nitrile warhead conferes additional advantadges to this inhibitor.
“Near Field Clues”, uz Ģeolokāciju un NFC tehnoloģijām balstīta izpētes spēle
2016
Hermaņa Verhoustinska kvalifikācijas darbā – “Near Field Clues”, uz Ģeolokāciju un NFC tehnoloģijām balstīta izpētes spēle – ir izstrādāta divplatformu lietotne Windows un Android lietotājiem. Lietotnes mērķis – nodrošināt izklaidējošu un virtuāli atalgojošu spēli, kas tās lietotājus mudinātu izpētīt un apmeklēt dažādus punktus pasaulē. Lietotne balstās uz divām galvenajām tehnoloģijām – Ģeolokāciju (tehnoloģija, kas izmantojot GPS un citus atrašanās vietas risinājumus, var noteikt ierīces atrašanās vietu uz Zemes divdimensiju plaknē) un NFC(ļoti nelielu attālumu bezvadu datu pārraides tehnoloģija). Izmantojot šis tehnoloģijas kvalifikācijas darbā izstrādātais risinājums ļauj lietotājiem ie…
Klientu apkalpošanas centru informācijas integrācija Oracle datu noliktavā
2015
Klientu apkalpošanas centru informācijas integrācija Oracle datu noliktavā ir daļa no uzņēmuma datu ielādes procesa. Darbā aprakstīts klientu apkalpošanas centru datu ielādes process un atskaites. Darbs realizēts izmantojot Oracle Data Integrator 11g un Oracle Buisness Intelligence Enterprise Edition 11g. Kvalifikācijas darbā iekļauta programmatūras prasību specifikācija, programmatūras projektējuma apraksts, testēšanas dokumentācija, programmatūras projekta pārvaldība, kvalitātes nodrošināšana, konfigurācijas pārvaldība, darbietilpības novērtējums, izmantotā literatūra un pielikums. Pielikumā pievienots: programmatūras koda piemērs, XML faili un tiem atbilstošās XML shēmas.
Predictive modeling of aryl hydrocarbon receptor (AhR) agonism
2020
Abstract The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of gene expression in metabolic machinery and detoxification systems. In the recent years, this receptor has attracted interest as a therapeutic target for immunological, oncogenic and inflammatory conditions. In the present report, in silico and in vitro approaches were combined to study the activation of the AhR. To this end, a large database of chemical compounds with known AhR agonistic activity was employed to build 5 classifiers based on the Adaboost (AdB), Gradient Boosting (GB), Random Forest (RF), Multilayer Perceptron (MLP) and Support Vector Machine (SVM) algorithms, respectively. The built classifier…
Active queue management stability in multiple bottleneck networks
2004
In this paper, we show that the active queue management (AQM) controllers, usually configured on a single bottleneck basis, may not prevent instability in the presence of multiple bottlenecks. We justify this result through a multiple bottleneck model.
Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods
2015
The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamiltonians. This enzyme catalyzes not only the dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate but also catalyzes racemization of different acylamino acids, with N-succinyl-R-phenylglycine being the best substrate. We investigated the molecular mechanisms for both reactions exploring the potential energy surface. Then, molecular dynamics simulations were performed to obtain the free energy profiles and the averaged interaction energies of enzymatic residues wi…
A QM/MM study of the reaction mechanism for the 3′-processing step catalyzed by HIV-1 integrase
2009
Integrase (IN) is one of the three human immunodeficiency virus type 1 enzymes (HIV-1) essential for effective viral replication. This viral enzyme is involved in the integration of HIV DNA into host chromosomal DNA. In this work we have carried out molecular dynamics simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach to study the reaction mechanism for the 3′-processing step of DNA integration using a model substrate. The results obtained by QM(AM1)/MM and QM(PM3)/MM simulations have been improved by single-point corrections using an ab initio method to describe the quantum subsystem. The results obtained within this computational model can be used to obtain …
Compartmental analysis of dynamic nuclear medicine data: Models and identifiability
2016
Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how non-linear regularization schemes can be applied t…