Optimisation of human VH domain antibodies specific to Mycobacterium tuberculosis heat shock protein (HSP16.3).

abstract：:We have undertaken molecular dynamics simulations on the d(CGCAAAAAAGCG).d(CGCTTTTTTGCG) dodecamer in solution. In this study, we focus on aspects of conformation and dynamics, including the possibility of cross-strand hydrogen bonds. We compare our results with those from crystallography as well as infrared, Raman an...

journal_title：Journal of computer-aided molecular design

authors： de Souza ON,Goodfellow JM

更新日期：1994-06-01 00:00:00

abstract：:A set of algorithms designed to enhance the display of protein binding cavities is presented. These algorithms, collectively entitled CAVITY SEARCH, allow the user to isolate and fully define the extent of a particular cavity. Solid modeling techniques are employed to produce a detailed cast of the active site region,...

journal_title：Journal of computer-aided molecular design

authors： Ho CM,Marshall GR

更新日期：1990-12-01 00:00:00

abstract：:Molecular modeling methodologies such as molecular docking, pharmacophore modeling, and 3D-QSAR, rely on conformational searches of small molecules as a starting point. All of these methodologies seek conformations of the small molecules as they bind to target proteins, i.e., their active conformations. Thus the quest...

journal_title：Journal of computer-aided molecular design

authors： Diller DJ,Merz KM Jr

更新日期：2002-02-01 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：: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：:All-atom molecular dynamics computer simulations were used to blindly predict the hydration free energies of a range of chloro-organic compounds as part of the SAMPL3 challenge. All compounds were parameterized within the framework of the OPLS-AA force field, using an established protocol to compute the absolute hydra...

journal_title：Journal of computer-aided molecular design

authors： Beckstein O,Iorga BI

更新日期：2012-05-01 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：:Estimation of bioavailability and toxicity at the very beginning of the drug development process is one of the big challenges in drug discovery. Most of the processes involved in ADME are driven by rather unspecific interactions between drugs and biological macromolecules. Within the past decade, drug transport pumps ...

journal_title：Journal of computer-aided molecular design

authors： Klein C,Kaiser D,Kopp S,Chiba P,Ecker GF

更新日期：2002-11-01 00:00:00

abstract：:We present blind predictions submitted to the SAMPL5 challenge on calculating distribution coefficients. The predictions were based on estimating the solvation free energies in water and cyclohexane of the 53 compounds in the challenge. These free energies were computed using alchemical free energy simulations based o...

journal_title：Journal of computer-aided molecular design

authors： Genheden S,Essex JW

更新日期：2016-11-01 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：:Non-canonical base pairs contribute immensely to the structural and functional variability of RNA, which calls for a detailed characterization of their spatial conformation. Intra-base pair parameters, namely propeller, buckle, open-angle, stagger, shear and stretch describe structure of base pairs indicating planarit...

journal_title：Journal of computer-aided molecular design

authors： Mukherjee S,Bansal M,Bhattacharyya D

更新日期：2006-10-01 00:00:00

abstract：:Accurate and well-curated experimental pKa data of organic acids and bases in both aqueous and non-aqueous media are invaluable in many areas of chemical research, including pharmaceutical, agrochemical, specialty chemical and property prediction research. In pharmaceutical research, pKa data are relevant in ligand de...

journal_title：Journal of computer-aided molecular design

authors： Slater AM

更新日期：2014-10-01 00:00:00

abstract：:A method has been developed that allows one to drive a molecule to conformations of lowest energy given the starting conformation, the identity of the rotatable bonds and the step size. This method has proved useful in our hands in the drug design arena where it is frequently more important to get 'low-energy' conform...

journal_title：Journal of computer-aided molecular design

authors： Jaeger EP,Peterson ML,Treasurywala AM

更新日期：1995-02-01 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：: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：:Molecular dynamics simulations of complexes between Norwalk virus RNA dependent RNA polymerase and its natural CTP and 2dCTP (both containing the O5'-C5'-C4'-O4' sequence of atoms bridging the triphosphate and sugar moiety) or modified coCTP (C5'-O5'-C4'-O4'), cocCTP (C5'-O5'-C4'-C4'') substrates were produced by mean...

journal_title：Journal of computer-aided molecular design

authors： Maláč K,Barvík I

更新日期：2013-04-01 00:00:00

abstract：:Activity cliffs are formed by pairs or groups of structurally similar compounds with significant differences in potency. They represent a prominent feature of activity landscapes of compound data sets and a primary source of structure-activity relationship (SAR) information. Thus far, activity cliffs have only been co...

journal_title：Journal of computer-aided molecular design

authors： Hu Y,Maggiora GM,Bajorath J

更新日期：2013-02-01 00:00:00

abstract：:As part of the fourth statistical assessment of modeling of proteins and ligands (sampl.eyesopen.com) prediction challenge, the strength of association of nine guests (1-9) binding to octa-acid host was determined by a combination of (1)H NMR and isothermal titration calorimetry. Association constants in sodium tetrab...

journal_title：Journal of computer-aided molecular design

authors： Gibb CL,Gibb BC

更新日期：2014-04-01 00:00:00

abstract：:This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empiric...

journal_title：Journal of computer-aided molecular design

authors： Murray CW,Auton TR,Eldridge MD

更新日期：1998-09-01 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：:De novo ligand design supports the search for novel molecular scaffolds in medicinal chemistry projects. This search can either be based on structural information of the targeted active site (structure-based approach) or on similarity to known binders (ligand-based approach). In the absence of structural information o...

journal_title：Journal of computer-aided molecular design

authors： Lippert T,Schulz-Gasch T,Roche O,Guba W,Rarey M

更新日期：2011-10-01 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：:The process of compound selection and prioritization is crucial for both combinatorial chemistry (CBC) and high throughput screening (HTS). Compound libraries have to be screened for unwanted chemical structures, as well as for unwanted chemical properties. Property extrema can be eliminated by using property filters,...

journal_title：Journal of computer-aided molecular design

authors： Oprea TI

更新日期：2000-03-01 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：:Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic p...

journal_title：Journal of computer-aided molecular design

authors： Tsvetkov VB,Serbin AV

更新日期：2012-12-01 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：:A method is suggested to calculate improved entropies within the MM/PBSA approach (molecular mechanics combined with Poisson-Boltzmann and surface area calculations) to estimate protein-ligand binding affinities. In the conventional approach, the protein is truncated outside ~8 A from the ligand. This system is freely...

journal_title：Journal of computer-aided molecular design

authors： Kongsted J,Ryde U

更新日期：2009-02-01 00:00:00

abstract：:Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development...

journal_title：Journal of computer-aided molecular design

authors： Beck B,Seeliger D,Kriegl JM

更新日期：2015-09-01 00:00:00

abstract：:Here, we report our results from quantitative structure-activity relationship studies on tyrosinase inhibitors. Interactions between benzoic acid derivatives and tyrosinase active sites were also studied using a molecular docking method. These studies indicated that one possible mechanism for the interaction between b...

journal_title：Journal of computer-aided molecular design

authors： Xue CB,Luo WC,Ding Q,Liu SZ,Gao XX

更新日期：2008-05-01 00:00:00

abstract：:The preferential occurrence of certain disulphide-bridge topologies in proteins has prompted us to design a method and a program, KNOT-MATCH, for their classification. The program has been applied to a database of proteins with less than 65% homology and more than two disulphide bridges. We have investigated whether t...

journal_title：Journal of computer-aided molecular design

authors： Mas JM,Aloy P,Martí-Renom MA,Oliva B,de Llorens R,Avilés FX,Querol E

更新日期：2001-05-01 00:00:00