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- Volume 19, Issue 23, 2013
Current Pharmaceutical Design - Volume 19, Issue 23, 2013
Volume 19, Issue 23, 2013
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Potential Application of Network Descriptions for Understanding Conformational Changes and Protonation States of ABC Transporters
Authors: Tamas Hegedus, Gergely Gyimesi, Merse E. Gaspar, Kristof Z. Szalay, Rajeev Gangal and Peter CsermelyThe ABC (ATP Binding Cassette) transporter protein superfamily comprises a large number of ubiquitous and functionally versatile proteins conserved from archaea to humans. ABC transporters have a key role in many human diseases and also in the development of multidrug resistance in cancer and in parasites. Although a dramatic progress has been achieved in ABC protein studies in the last decades, we ar Read More
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Protonation States in Molecular Dynamics Simulations of Peptide Folding and Binding
Authors: Avraham Ben-Shimon, Deborah E. Shalev and Masha Y. NivPeptides are important signaling modules, acting both as individual hormones and as parts of larger molecules, mediating their protein-protein interactions. Many peptidic and peptidomimetic drugs have reached the marketplace and opportunities for peptide-based drug discovery are on the rise. pH-dependent behavior of peptides is well documented in the context of misfolding diseases and peptide translocation. Changes in Read More
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The Role of Protonation States in Ligand-Receptor Recognition and Binding
Authors: Marharyta Petukh, Shannon Stefl and Emil AlexovIn this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa’s and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pHdependence of the binding. Inde Read More
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Intrinsic Disorder-based Protein Interactions and their Modulators
More LessIt is clear now that proteins lacking ordered structure, generally known as intrinsically disordered proteins (IDPs), possess numerous biological functions that complement functional repertoires of ordered proteins. IDPs are common in nature, and abundantly found to be involved in the pathogenesis of various diseases. These proteins participate in various biological processes and play crucial roles in regulation of functio Read More
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Nucleotide Binding Affects Intrinsic Dynamics and Structural Communication in Ras GTPases
Authors: Francesca Fanelli and Francesco RaimondiThe Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. These proteins act biologically as molecular switches, which, cycling between OFF and ON states, play fundamental role in cell biology. This review article summarizes the inferences from the widest computational analyses done so far on Ras GTPases aimed at providing a comprehensive str Read More
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Resolving Differences in Substrate Specificities between Human and Parasite Phosphoribosyltransferases via Analysis of Functional Groups of Substrates and Receptors
Authors: Zofia Gasik, David Shugar and Jan M. AntosiewiczWe herein review experimental and theoretical approaches widely applied to delineation of the differences in substrate specificities between human and parasite phosphoribosyltransferases (PRTases), the latter of which are key targets for treatment of diseases caused by parasites. Standard Molecular Dynamics (MD) simulations have been applied to determine why the human PRTase prefers guanine over xanthine, whereas t Read More
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Protein: Ligand Recognition: Simple Models for Electrostatic Effects
More LessFree energy simulations are a powerful tool to study molecular recognition. The most rigorous variants can provide in depth understanding for a particular system, but are not suited for high throughput application to large libraries of compounds. Related, but less expensive methods are increasingly popular, including continuum electrostatic methods like PBSA (""Poisson-Boltzmann Surface Area") and Linear Response or L Read More
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On the Active Site Protonation State in Aspartic Proteases: Implications for Drug Design
Authors: Fredy Sussman, M. Carmen Villaverde, Jose L. Dominguez and U. Helena DanielsonAspartic proteases (AP) are a family of important hydrolytic enzymes in medicinal chemistry, since many of its members have become therapeutical targets for a wide variety of diseases from AIDS to Alzheimer. The enzymatic activity of these proteins is driven by the Asp dyad, a pair of active site Asp residues that participate in the hydrolysis of peptides. Hence, the protonation state of these and other acidic resid Read More
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Effects of the Protonation State of the Catalytic Residues and Ligands Upon Binding and Recognition in Targeted Proteins of HIV-1 and Influenza Viruses
More LessThe determination of the protonation state of the functional groups of ligands, and the amino acid residues with electrically charged side chains (His, Lys, Arg, Asp and Glu) or the nucleotide bases of the nucleic acids that they interact with, is important for ligand binding and recognition, the enzyme activity and reaction mechanism, and protein folding/unfolding and stability. Herein, the effects of different protonation state as Read More
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Correct Protonation States and Relevant Waters = Better Computational Simulations?
Authors: Francesca Spyrakis, Luca Dellafiora, Chenxiao Da, Glen E. Kellogg and Pietro CozziniThe unique physicochemical properties of water make it the most important molecule for life. Water molecules have many roles, direct and indirect, related to both biological structure and function. This paper: 1) reviews tools for the prediction of water conservation in and around protein active sites, by empirical (knowledge-based) algorithms and by methods based on thermodynamics principles; 2) reviews principles and Read More
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Calculation Methods for the Enhancement of Pharmaceutical Properties in Small Molecules: Estimating the Cationic pKa
Authors: Ann R. Hermone and Rick GussioIn this review, a summary of methodologies is covered to enable medicinal chemists to access an overview of pKa estimation devices. In order to stave overutilization of costly synthetic resources, the chemist requires an accurate and computationally tractable solution for estimating a pKa of a candidate molecule. We focus on the cationic moieties, since they are so fundamentally important in the chemistry of drugs, and poss Read More
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Rigorous Incorporation of Tautomers, Ionization Species, and Different Binding Modes into Ligand-Based and Receptor-Based 3D-QSAR Methods
Authors: Senthil Natesan and Stefan BalazSpeciation of drug candidates and receptors caused by ionization, tautomerism, and/or covalent hydration complicates ligandand receptor-based predictions of binding affinities by 3-dimensional structure-activity relationships (3D-QSAR). The speciation problem is exacerbated by tendency of tautomers to bind in multiple conformations or orientations (modes) in the same binding site. New forms of the 3D-QSAR correlation eq Read More
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Protonation States and Conformational Ensemble in Ligand-based QSAR Modeling
More LessDrug affinity and function depend on the different protonation species (present in the biological context) that generate different conformational ensembles with different structural features and, hence, different physico-chemical properties. In the present review article these strongly interdependent structural features will be considered for their crucial role in ligand-based QSAR modeling and drug design by using qua Read More
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
- Issue 42
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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