abstract：:Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force ...

journal_title：Journal of computer-aided molecular design

authors： Ehrman JN,Lim VT,Bannan CC,Thi N,Kyu DY,Mobley DL

更新日期：2021-01-28 00:00:00

abstract：:In the context of the SAMPL7 challenge, we computed, employing a non-equilibrium (NE) alchemical technique, the standard binding free energy of two series of host-guest systems, involving as a host the Isaac's TrimerTrip, a Cucurbituril-like open cavitand, and the Gilson's Cyclodextrin derivatives. The adopted NE alch...

journal_title：Journal of computer-aided molecular design

authors： Procacci P,Guarnieri G

更新日期：2021-01-04 00:00:00

abstract：:Anaplastic lymphoma kinase (ALK) has been thought to be a prospective target of anti-drug resistance design in treatment of tumors and specific neuron diseases. It is highly useful for the seeking of possible strategy alleviating drug resistance to probe the mutation-mediated effect on binding of inhibitors to ALK. In...

journal_title：Journal of computer-aided molecular design

authors： Chen J,Wang W,Sun H,Pang L,Yin B

更新日期：2020-12-01 00:00:00

abstract：:The free fatty acid receptor 1 (FFAR1, formerly GPR40), is a potential G protein-coupled receptor (GPCR) target for the treatment of type 2 diabetes mellitus (T2DM), as it enhances glucose-dependent insulin secretion upon activation by endogenous long-chain free fatty acids. The presence of two allosterically communic...

journal_title：Journal of computer-aided molecular design

authors： Atanasio S,Deganutti G,Reynolds CA

更新日期：2020-11-01 00:00:00

abstract：:The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs appr...

journal_title：Journal of computer-aided molecular design

authors： Deganutti G,Prischi F,Reynolds CA

更新日期：2020-10-26 00:00:00

abstract：:Drug discovery is an expensive and time-consuming process. To make this process more efficient quantum chemistry methods can be employed. The electrophilicity index is one property that can be calculated by quantum chemistry methods, and if calculated correctly gives insight into the reactivity of covalent inhibitors....

journal_title：Journal of computer-aided molecular design

authors： Hermann MR,Pautsch A,Grundl MA,Weber A,Tautermann CS

更新日期：2020-10-05 00:00:00

abstract：:Optimization in medicinal chemistry often involves designing replacements for a section of a molecule which aim to retain potency while improving other properties of the compound. In this study, we perform a retrospective analysis using a number of computational methods to identify active side chains amongst a pool of...

journal_title：Journal of computer-aided molecular design

authors： Baumgartner MP,Evans DA

更新日期：2020-09-01 00:00:00

abstract：:In contrast to the computational generation of conventional tautomers, the analogous operation that would produce ring-chain tautomers is rarely available in cheminformatics codes. This is partly due to the perceived unimportance of ring-chain tautomerism and partly because specialized algorithms are required to reali...

journal_title：Journal of computer-aided molecular design

authors： Levine DS,Watson MA,Jacobson LD,Dickerson CE,Yu HS,Bochevarov AD

更新日期：2020-08-24 00:00:00

abstract：:Cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Since they are connected to drug interactions, screening for potential inhibitors is of utmost importance in drug discovery settings. Our study provides an extensive classification model for P450-drug interactions with one of the mo...

journal_title：Journal of computer-aided molecular design

authors： Rácz A,Keserű GM

更新日期：2020-08-01 00:00:00

abstract：:The pKa is the standard measure used to describe the aqueous proton affinity of a compound, indicating the proton concentration (pH) at which two protonation states (e.g. A- and AH) have equal free energy. However, compounds can have additional protonation states (e.g. AH2+), and may assume multiple tautomeric forms, ...

journal_title：Journal of computer-aided molecular design

authors： Gunner MR,Murakami T,Rustenburg AS,Işık M,Chodera JD

更新日期：2020-05-01 00:00:00

abstract：:Two different types of approaches: (a) approaches that combine quantitative structure activity relationships, quantum mechanical electronic structure methods, and machine-learning and, (b) electronic structure vertical solvation approaches, were used to predict the logP coefficients of 11 molecules as part of the SAMP...

journal_title：Journal of computer-aided molecular design

authors： Patel P,Kuntz DM,Jones MR,Brooks BR,Wilson AK

更新日期：2020-05-01 00:00:00

abstract：:The Drug Design Data Resource (D3R) Grand Challenges present an opportunity to assess, in the context of a blind predictive challenge, the accuracy and the limits of tools and methodologies designed to help guide pharmaceutical drug discovery projects. Here, we report the results of our participation in the D3R Grand ...

journal_title：Journal of computer-aided molecular design

authors： Sasmal S,El Khoury L,Mobley DL

更新日期：2020-02-01 00:00:00

abstract：:In this paper we describe our approaches to predict the binding mode of twenty BACE1 ligands as part of Grand Challenge 4 (GC4), organized by the Drug Design Data Resource. Calculations for all submissions (except for one, which used AutoDock4.2) were performed using AutoDock-GPU, the new GPU-accelerated version of Au...

journal_title：Journal of computer-aided molecular design

authors： Santos-Martins D,Eberhardt J,Bianco G,Solis-Vasquez L,Ambrosio FA,Koch A,Forli S

更新日期：2019-12-01 00:00:00

abstract：:Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to bui...

journal_title：Journal of computer-aided molecular design

authors： Cardoso-Silva J,Papageorgiou LG,Tsoka S

更新日期：2019-09-01 00:00:00

abstract：:The kinase-regulatory cell signaling networks play a central role in the pathogenesis of human cervical cancer (hCC). However, only few kinase inhibitors have been successfully developed for treatment of this cancer to date. Considering that the active sites of protein kinases are highly conserved and small-molecule i...

journal_title：Journal of computer-aided molecular design

authors： Han M,Sun D

更新日期：2019-07-01 00:00:00

abstract：:Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA-RNA/protein interaction sites are of increasing importance as potential targets for new m...

journal_title：Journal of computer-aided molecular design

authors： Yamasaki S,Amemiya T,Yabuki Y,Horimoto K,Fukui K

更新日期：2019-05-01 00:00:00

abstract：:SIRT1 is an NAD+-dependent deacetylase, whose activators have potential therapeutic applications in the age-related, metabolic, neurode-generative and cardiovascular diseases. Resveratrol (RSV) has been regarded as potent SIRT1 activator in the treatment of atherosclerosis and cardiovascular diseases. Moreover, the pr...

journal_title：Journal of computer-aided molecular design

authors： Chen H,Wang Y,Gao Z,Yang W,Gao J

更新日期：2019-04-01 00:00:00

abstract：:Mycobacterium tuberculosis (Mtb) 16.3 kDa heat shock protein 16.3 (HSP16.3) is a latency-associated antigen that can be targeted for latent tuberculosis (TB) diagnostic and therapeutic development. We have previously developed human VH domain antibodies (dAbs; clone E3 and F1) specific against HSP16.3. In this work, w...

journal_title：Journal of computer-aided molecular design

authors： Soong JX,Chan SK,Lim TS,Choong YS

更新日期：2019-03-01 00:00:00

abstract：:The worldwide spread of beta-lactamases with hydrolytic activity extended to last resort carbapenems is aggravating the antibiotic resistance problem and endangers the successful antimicrobial treatment of clinically relevant pathogens. As recently highlighted by the World Health Organization, new strategies to contai...

journal_title：Journal of computer-aided molecular design

authors： Spyrakis F,Bellio P,Quotadamo A,Linciano P,Benedetti P,D'Arrigo G,Baroni M,Cendron L,Celenza G,Tondi D

更新日期：2019-02-01 00:00:00

abstract：:During the last few years, we have developed a docking protocol involving two steps: (i) the choice of the most appropriate docking software and parameters for the system of interest using structural and functional information available in public databases (PDB, ChEMBL, PubChem Assay, BindingDB, etc.); (ii) the dockin...

journal_title：Journal of computer-aided molecular design

authors： Chaput L,Selwa E,Elisée E,Iorga BI

更新日期：2019-01-01 00:00:00

abstract：:Manifold representations of rotational/translational motion and conformational space of a ligand were previously shown to be effective for local energy optimization. In this paper we report the development of the Monte-Carlo energy minimization approach (MCM), which uses the same manifold representation. The approach ...

journal_title：Journal of computer-aided molecular design

authors： Ignatov M,Liu C,Alekseenko A,Sun Z,Padhorny D,Kotelnikov S,Kazennov A,Grebenkin I,Kholodov Y,Kolosvari I,Perez A,Dill K,Kozakov D

更新日期：2019-01-01 00:00:00

abstract：:Feature selection is commonly used as a preprocessing step to machine learning for improving learning performance, lowering computational complexity and facilitating model interpretation. This paper proposes the application of boosting feature selection to improve the classification performance of standard feature sel...

journal_title：Journal of computer-aided molecular design

authors： Cerruela García G,García-Pedrajas N

更新日期：2018-11-01 00:00:00

abstract：:Macroscopic pKa values were calculated for all compounds in the SAMPL6 blind prediction challenge, based on quantum chemical calculations with a continuum solvation model and a linear correction derived from a small training set. Microscopic pKa values were derived from the gas-phase free energy difference between pro...

journal_title：Journal of computer-aided molecular design

authors： Selwa E,Kenney IM,Beckstein O,Iorga BI

更新日期：2018-10-01 00:00:00

abstract：:The "embedded cluster reference interaction site model" (EC-RISM) integral equation theory is applied to the problem of predicting aqueous pKa values for drug-like molecules based on an ensemble of tautomers. EC-RISM is based on self-consistent calculations of a solute's electronic structure and the distribution funct...

journal_title：Journal of computer-aided molecular design

authors： Tielker N,Eberlein L,Güssregen S,Kast SM

更新日期：2018-10-01 00:00:00

abstract：:We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone. The method is closely related to the QMOD approach, substituting a learned scoring field for a pocket constructed of molecular fragments. The problem of mutual ligand a...

journal_title：Journal of computer-aided molecular design

authors： Cleves AE,Jain AN

更新日期：2018-07-01 00:00:00

abstract：:In the present study, the binding free energy of a family of huprines with acetylcholinesterase (AChE) is calculated by means of the free energy perturbation method, based on hybrid quantum mechanics and molecular mechanics potentials. Binding free energy calculations and the analysis of the geometrical parameters hig...

journal_title：Journal of computer-aided molecular design

authors： Nascimento ÉCM,Oliva M,Andrés J

更新日期：2018-05-01 00:00:00

abstract：:Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze da...

journal_title：Journal of computer-aided molecular design

authors： Raschka S,Wolf AJ,Bemister-Buffington J,Kuhn LA

更新日期：2018-04-01 00:00:00

abstract：:The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less acti...

journal_title：Journal of computer-aided molecular design

authors： Sanusi ZK,Govender T,Maguire GEM,Maseko SB,Lin J,Kruger HG,Honarparvar B

更新日期：2018-03-01 00:00:00

abstract：:In virtual drug screening, the chemical diversity of hits is an important factor, along with their predicted activity. Moreover, interim results are of interest for directing the further research, and their diversity is also desirable. In this paper, we consider a problem of obtaining a diverse set of virtual screenin...

journal_title：Journal of computer-aided molecular design

authors： Nikitina N,Ivashko E,Tchernykh A

更新日期：2018-02-01 00:00:00

abstract：:We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource ( https://drugdesigndata.org/ ). The challenge was focused on the ligands of the farnesoid X rece...

journal_title：Journal of computer-aided molecular design

authors： Yakovenko O,Jones SJM

更新日期：2018-01-01 00:00:00

abstract：:We describe the performance of multiple pose prediction methods for the D3R 2016 Grand Challenge. The pose prediction challenge includes 36 ligands, which represent 4 chemotypes and some miscellaneous structures against the FXR ligand binding domain. In this study we use a mix of fully automated methods as well as hum...

journal_title：Journal of computer-aided molecular design

authors： Fradera X,Verras A,Hu Y,Wang D,Wang H,Fells JI,Armacost KA,Crespo A,Sherborne B,Wang H,Peng Z,Gao YD

更新日期：2018-01-01 00:00:00

abstract：:Computational protein binding affinity prediction can play an important role in drug research but performing efficient and accurate binding free energy calculations is still challenging. In the context of phase 2 of the Drug Design Data Resource (D3R) Grand Challenge 2 we used our automated eTOX ALLIES approach to app...

journal_title：Journal of computer-aided molecular design

authors： Rifai EA,van Dijk M,Vermeulen NPE,Geerke DP

更新日期：2018-01-01 00:00:00

abstract：:Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein-protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein-peptide interactions. Here, we report our latest attempt to expand the capabilities of t...

journal_title：Journal of computer-aided molecular design

authors： Padhorny D,Hall DR,Mirzaei H,Mamonov AB,Moghadasi M,Alekseenko A,Beglov D,Kozakov D

更新日期：2018-01-01 00:00:00

abstract：:Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility im...

journal_title：Journal of computer-aided molecular design

authors： Badalkhani-Khamseh F,Ebrahim-Habibi A,Hadipour NL

更新日期：2017-12-01 00:00:00

abstract：:ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are report...

journal_title：Journal of computer-aided molecular design

authors： Park I,Hwang YJ,Kim T,Viswanath ANI,Londhe AM,Jung SY,Sim KM,Min SJ,Lee JE,Seong J,Kim YK,No KT,Ryu H,Pae AN

更新日期：2017-10-01 00:00:00

abstract：:Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in pa...

journal_title：Journal of computer-aided molecular design

authors： Kunimoto R,Bajorath J

更新日期：2017-09-01 00:00:00

abstract：:The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by us...

journal_title：Journal of computer-aided molecular design

authors： Xu X,Yan C,Zou X

更新日期：2017-08-01 00:00:00

abstract：:There is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. Here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that ap...

journal_title：Journal of computer-aided molecular design

authors： Jedwabny W,Panecka-Hofman J,Dyguda-Kazimierowicz E,Wade RC,Sokalski WA

更新日期：2017-08-01 00:00:00

abstract：:Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibitio...

journal_title：Journal of computer-aided molecular design

authors： Fernández D,Ramis R,Ortega-Castro J,Casasnovas R,Vilanova B,Frau J

更新日期：2017-07-01 00:00:00

abstract：:Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases ...

journal_title：Journal of computer-aided molecular design

authors： Al-Dabbagh MM,Salim N,Himmat M,Ahmed A,Saeed F

更新日期：2017-04-01 00:00:00