Monte Carlo on the manifold and MD refinement for binding pose prediction of protein-ligand complexes: 2017 D3R Grand Challenge.

abstract：:The mounting evidences have shown that signal transducer and activator of transcription 3 (Stat3) is a critical target for cancer therapy. Recently, we developed a G-quartet oligonucleotide T40214 as a novel and potent Stat3 inhibitor. T40214 specifically inhibited DNA-binding activity of Stat3 and significantly suppr...

journal_title：Journal of computer-aided molecular design

authors： Zhu Q,Jing N

更新日期：2007-10-01 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：:We present three complementary approaches for score-tuning that improve docking performance in pose prediction, virtual screening and binding affinity assessment. The methodology utilizes experimental data to customize the scoring function for the system of interest considering the specific docking scenario. The tunin...

journal_title：Journal of computer-aided molecular design

authors： Ravitz O,Zsoldos Z,Simon A

更新日期：2011-11-01 00:00:00

abstract：:We have developed quantitative structure-activity relationship (QSAR) models for 44 non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of the pyridinone derivative type. The k nearest neighbor (kNN) variable selection approach was used. This method utilizes multiple descriptors such as molecular connectivi...

journal_title：Journal of computer-aided molecular design

authors： Medina-Franco JL,Golbraikh A,Oloff S,Castillo R,Tropsha A

更新日期：2005-04-01 00:00:00

abstract：:One of the most important pharmacological mechanisms of antimalarial action is the inhibition of the aggregation of hematin into hemozoin. We present a group of new potential antimalarial molecules for which we have performed a DFT study of their stereoelectronic properties. Additionally, the same calculations were ca...

journal_title：Journal of computer-aided molecular design

authors： Portela C,Afonso CM,Pinto MM,Ramos MJ

更新日期：2003-09-01 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 electron-conformational (EC) method in QSAR problems employs a unique (based on first principles) descriptor of molecular properties that incorporates the electronic structure and topology of the molecule and is presented in a digital-matrix form suitable for computer processing, the EC matrix of congruity (ECMC)....

journal_title：Journal of computer-aided molecular design

authors： Bersuker IB

更新日期：2008-06-01 00:00:00

abstract：:The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomer...

journal_title：Journal of computer-aided molecular design

authors： Cruz-Cabeza AJ,Schreyer A,Pitt WR

更新日期：2010-06-01 00:00:00

abstract：:The binding mode prediction is of great importance to structure-based drug design. The discrimination of various binding poses of ligand generated by docking is a great challenge not only to docking score functions but also to the relatively expensive free energy calculation methods. Here we systematically analyzed th...

journal_title：Journal of computer-aided molecular design

authors： Liu K,Watanabe E,Kokubo H

更新日期：2017-02-01 00:00:00

abstract：:Pharmacophore methods provide a way of establishing a structure activity relationship for a series of known active ligands. Often, there are several plausible hypotheses that could explain the same set of ligands and, in such cases, it is important that the chemist is presented with alternatives that can be tested wit...

journal_title：Journal of computer-aided molecular design

authors： Cottrell SJ,Gillet VJ,Taylor R,Wilton DJ

更新日期：2004-11-01 00:00:00

abstract：:Combining Lipinski's rule with the docking and steered molecular dynamics simulations and using the PubChem data base of about 1.4 million compounds, we have obtained DNA dyes Hoechst 34580 and Hoechst 33342 as top-leads for the Alzheimer's disease. The binding properties of these ligands to amyloid beta (Aβ) fibril w...

journal_title：Journal of computer-aided molecular design

authors： Thai NQ,Tseng NH,Vu MT,Nguyen TT,Linh HQ,Hu CK,Chen YR,Li MS

更新日期：2016-08-01 00:00:00

abstract：:4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazines have been discovered as inhibitors of p38alpha. Experimental assays have proven that the configuration of alpha-Me-benzyl connected with amide at C6 is essential for the binding affinity. The S-configured inhibitor (11j) displays 80 times more potency than the R-configure...

journal_title：Journal of computer-aided molecular design

authors： Chen Q,Cui W,Ji M

更新日期：2009-10-01 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：:Hydrogen bonds are the most specific, and therefore predictable of the intermolecular interactions involved in ligand-protein binding. Given the structure of a molecule, it is possible to estimate the positions at which complementary hydrogen-bonding atoms could be found. Crystal-survey data are used in the design of ...

journal_title：Journal of computer-aided molecular design

authors： Mills JE,Perkins TD,Dean PM

更新日期：1997-05-01 00:00:00

abstract：:To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the...

journal_title：Journal of computer-aided molecular design

authors： Perryman AL,Santiago DN,Forli S,Martins DS,Olson AJ

更新日期：2014-04-01 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：:A major problem in modelling (biological) macromolecules is the search for low-energy conformations. The complexity of a conformational search problem increases exponentially with the number of degrees of freedom which means that a systematic search can only be performed for very small structures. Here we introduce a ...

journal_title：Journal of computer-aided molecular design

authors： van Schaik RC,van Gunsteren WF,Berendsen HJ

更新日期：1992-04-01 00:00:00

abstract：:We developed a new structure-based in-silico screening method using a negative image of a ligand-binding pocket and a multi-protein-compound interaction matrix. Based on the structure of the ligand pocket of the target protein, we designed a negative image, which consists of virtual atoms whose radii are close to thos...

journal_title：Journal of computer-aided molecular design

authors： Fukunishi Y,Kubota S,Kanai C,Nakamura H

更新日期：2006-04-01 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：:We apply an atomistic model of passive membrane permeability to a series of weakly basic drugs. The computational model uses conformational sampling in combination with an all-atom force field and implicit solvent model to estimate relative passive membrane permeabilities. The model does not require the use of trainin...

journal_title：Journal of computer-aided molecular design

authors： Kalyanaraman C,Jacobson MP

更新日期：2007-12-01 00:00:00

abstract：:New methods for docking, template fitting and building pseudo-receptors are described. Full conformational searches are carried out for flexible cyclic and acyclic molecules. QXP (quick explore) search algorithms are derived from the method of Monte Carlo perturbation with energy minimization in Cartesian space. An ad...

journal_title：Journal of computer-aided molecular design

authors： McMartin C,Bohacek RS

更新日期：1997-07-01 00:00:00

abstract：:The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal...

journal_title：Journal of computer-aided molecular design

authors： Allen FH,Harris SE,Taylor R

更新日期：1996-06-01 00:00:00

abstract：:In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classi...

journal_title：Journal of computer-aided molecular design

authors： Czodrowski P

更新日期：2014-11-01 00:00:00

abstract：:The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-li...

journal_title：Journal of computer-aided molecular design

authors： Cheng A,Dixon SL

更新日期：2003-12-01 00:00:00

abstract：:Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of dockin...

journal_title：Journal of computer-aided molecular design

authors： Taha MO,Habash M,Khanfar MA

更新日期：2014-05-01 00:00:00

abstract：:Molecular structures and functions of the majority of proteins across different species are yet to be identified. Much needed functional annotation of these gene products often benefits from the knowledge of protein-ligand interactions. Towards this goal, we developed eFindSite, an improved version of FINDSITE, design...

journal_title：Journal of computer-aided molecular design

authors： Brylinski M,Feinstein WP

更新日期：2013-06-01 00:00:00

abstract：:RNA interference (RNAi) is a critical cellular pathway activated by double stranded RNA and regulates the gene expression of target mRNA. During RNAi, the 3' end of siRNA binds with the PAZ domain, followed by release and rebinding in a cyclic manner, which deemed essential for proper gene silencing. Recently, we prov...

journal_title：Journal of computer-aided molecular design

authors： Kandeel M,Kitade Y

更新日期：2013-07-01 00:00:00

abstract：:Clarithromycin (6-O-methylerythromycin A) is a 14-membered macrolide antibiotic which is active in vitro against clinically important gram-positive and gram-negative bacteria. The selectivity of the methylation of the C-6 OH group is studied on erythromycin A derivatives. To understand the effect of the solvent on the...

journal_title：Journal of computer-aided molecular design

authors： Duran D,Aviyente V,Baysa C

更新日期：2004-02-01 00:00:00

abstract：:A structure-binding activity relationship for the intestinal bile acid transporter has been developed using data from a series of bile acid analogs in a comparative molecular field analysis (CoMFA). The studied compounds consisted of a series of bile acid-peptide conjugates, with modifications at the 24 position of th...

journal_title：Journal of computer-aided molecular design

authors： Swaan PW,Szoka FC Jr,Oie S

更新日期：1997-11-01 00:00:00

abstract：:It is essential, in order to minimise expensive drug failures due to toxicity being found in late development or even in clinical trials, to determine potential toxicity problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening...

journal_title：Journal of computer-aided molecular design

authors： Dearden JC

更新日期：2003-02-01 00:00:00