The configurational dependence of binding free energies: a Poisson-Boltzmann study of Neuraminidase inhibitors.

abstract：:We have used virtual screening to develop models for the binding of aryl substituted heterocycles to p38α MAPK. Virtual screening was conducted on a number of p38α MAPK crystal structures using a library of 46 known p38α MAPK inhibitors containing a heterocyclic core substituted by pyridine and fluorophenyl rings (str...

journal_title：Journal of computer-aided molecular design

authors： Vinh NB,Simpson JS,Scammells PJ,Chalmers DK

更新日期：2012-04-01 00:00:00

abstract：:Cheminformatics protocols have been developed and assessed that identify a small set of fragments which can represent the compounds in a chemical library for use in fragment-based ligand discovery. Six different methods have been implemented and tested on Input Libraries of compounds from three suppliers. The resultin...

journal_title：Journal of computer-aided molecular design

authors： Schulz MN,Landström J,Bright K,Hubbard RE

更新日期：2011-07-01 00:00:00

abstract：:Benchmarks for molecular docking have historically focused on re-docking the cognate ligand of a well-determined protein-ligand complex to measure geometric pose prediction accuracy, and measurement of virtual screening performance has been focused on increasingly large and diverse sets of target protein structures, c...

journal_title：Journal of computer-aided molecular design

authors： Spitzer R,Jain AN

更新日期：2012-06-01 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：: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：: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：:Aromatic amino acid residues are often present in carbohydrate-binding sites of proteins. These binding sites are characterized by a placement of a carbohydrate moiety in a stacking orientation to an aromatic ring. This arrangement is an example of CH/pi interactions. Ab initio interaction energies for 20 carbohydrate...

journal_title：Journal of computer-aided molecular design

authors： Spiwok V,Lipovová P,Skálová T,Vondrácková E,Dohnálek J,Hasek J,Králová B

更新日期：2005-12-01 00:00:00

abstract：:Computational prediction of the effects of residue changes on peptide-protein binding affinities, followed by experimental testing of the top predicted binders, is an efficient strategy for the rational structure-based design of peptide inhibitors. In this study we apply this approach to the discovery of competitive a...

journal_title：Journal of computer-aided molecular design

authors： Te JA,Dong M,Miller LJ,Bordner AJ

更新日期：2012-07-01 00:00:00

abstract：:The de novo design program Skelgen has been used to design inhibitor structures for four targets of pharmaceutical interest. The designed structures are compared to modeled binding modes of known inhibitors (i) visually and (ii) by means of a novel similarity measure considering the size and spatial proximity of the m...

journal_title：Journal of computer-aided molecular design

authors： Stahl M,Todorov NP,James T,Mauser H,Boehm HJ,Dean PM

更新日期：2002-07-01 00:00:00

abstract：:Two new continuum solvation models have been presented recently, and in this paper they are explained and reviewed in detail with further examples. Solvation Model 2 (AM1-SM2) is based on the Austin Model 1 and Solvation Model 3 (PM3-SM3) on the Parameterized Model 3 semiempirical Hamiltonian. In addition to the incor...

journal_title：Journal of computer-aided molecular design

authors： Cramer CJ,Truhlar DG

更新日期：1992-12-01 00:00:00

abstract：:A new type of shape descriptor is proposed to describe the spatial orientation for non-covalent interactions. It is built from simple, anisotropic Gaussian contributions that are parameterised by 10 adjustable values. The descriptors have been used to fit propensity distributions derived from scatter data stored in th...

journal_title：Journal of computer-aided molecular design

authors： Nissink JWM,Verdonk ML,Klebe G

更新日期：2000-11-01 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：:Thirty-six compounds, representing six different structural classes of insecticides which are known to act at the gamma-aminobutyric acid receptor/chloride ionophore, have been superimposed by methods which maximise the commonality of steric and electrostatic fields. Maximal steric and electrostatic alignment was deri...

journal_title：Journal of computer-aided molecular design

authors： Calder JA,Wyatt JA,Frenkel DA,Casida JE

更新日期：1993-02-01 00:00:00

abstract：:Ligand efficiency metrics are used in drug discovery to normalize biological activity or affinity with respect to physicochemical properties such as lipophilicity and molecular size. This Perspective provides an overview of ligand efficiency metrics and summarizes thermodynamics of protein-ligand binding. Different cl...

journal_title：Journal of computer-aided molecular design

authors： Kenny PW,Leitão A,Montanari CA

更新日期：2014-07-01 00:00:00

abstract：:Chemical space networks (CSNs) have recently been introduced as an alternative to other coordinate-free and coordinate-based chemical space representations. In CSNs, nodes represent compounds and edges pairwise similarity relationships. In addition, nodes are annotated with compound property information such as biolog...

journal_title：Journal of computer-aided molecular design

authors： Zhang B,Vogt M,Maggiora GM,Bajorath J

更新日期：2015-10-01 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：: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：: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：:Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume o...

journal_title：Journal of computer-aided molecular design

authors： van de Waterbeemd H,Smith DA,Jones BC

更新日期：2001-03-01 00:00:00

abstract：:Molecular modeling techniques and three-dimensional (3D) pattern analysis have been used to investigate the chemical and steric properties of compounds that inhibit transport of the plant hormone auxin. These compounds bind to a specific site on the plant plasma membrane characterized by its affinity for the herbicide...

journal_title：Journal of computer-aided molecular design

authors： Bures MG,Black-Schaefer C,Gardner G

更新日期：1991-08-01 00:00:00

abstract：:Utilization of coupling constants as restraints in computational structure refinement is reviewed. In addition, we address the effect of conformational averaging and examine different approaches to apply the restraints when the experimental observable is obviously a result of averaging. Here, two different computation...

journal_title：Journal of computer-aided molecular design

authors： Mierke DF,Huber T,Kessler H

更新日期：1994-02-01 00:00:00

abstract：:Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds...

journal_title：Journal of computer-aided molecular design

authors： Tomić S,Gabdoulline RR,Kojić-Prodić B,Wade RC

更新日期：1998-01-01 00:00:00

abstract：:Overexpression of Bcl-2 and Bcl-xL proteins, both inhibitors of apoptosis or programmed cell death, is related to the generation and development of several types of cancer as well as to an elevated resistance to chemotherapeutic treatments. Given that synthetic peptide fragments of the BH3 domain are capable to bind t...

journal_title：Journal of computer-aided molecular design

authors： Pinto M,Perez JJ,Rubio-Martinez J

更新日期：2004-01-01 00:00:00

abstract：:In the present work we have modeled the Michaelis complex of the cyclic-Adenosine Monophosphate Dependent (cAMD) Protein Kinase A (PKA) with Mg(2)ATP and the heptapeptide substrate Kemptide by classical molecular dynamics. The chosen synthetic substrate is relevant for its high efficiency and small size, and it has no...

journal_title：Journal of computer-aided molecular design

authors： Montenegro M,Garcia-Viloca M,González-Lafont A,Lluch JM

更新日期：2007-10-01 00:00:00

abstract：:Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate...

journal_title：Journal of computer-aided molecular design

authors： Riniker S,Barandun LJ,Diederich F,Krämer O,Steffen A,van Gunsteren WF

更新日期：2012-12-01 00:00:00

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：: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：:An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which w...

journal_title：Journal of computer-aided molecular design

authors： Schneider G,Lee ML,Stahl M,Schneider P

更新日期：2000-07-01 00:00:00

abstract：:Using the X-ray crystal structure of the human topoisomerase I (top1) - DNA cleavable complex and the Sybyl software package, we have developed a general model for the ternary cleavable complex formed with four protoberberine alkaloids differing in the substitution on the terminal phenyl rings and covering a broad ran...

journal_title：Journal of computer-aided molecular design

authors： Kettmann V,Kost'álová D,Höltje HD

更新日期：2004-12-01 00:00:00

abstract：:In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means ...

journal_title：Journal of computer-aided molecular design

authors： Romanelli MN,Dei S,Scapecchi S,Teodori E,Gualtieri F,Budriesi R,Mannhold R

更新日期：1994-04-01 00:00:00