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 were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were modeled in two low-energy conformations, 'P' and 'T', so as to obtain the best match to the 'planar' and 'tilted' conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Tomić S,Gabdoulline RR,Kojić-Prodić B,Wade RCdoi
10.1023/a:1007973008558subject
Has Abstractpub_date
1998-01-01 00:00:00pages
63-79issue
1eissn
0920-654Xissn
1573-4951journal_volume
12pub_type
杂志文章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
pub_type： 杂志文章
doi：10.1007/s10822-018-0161-7
更新日期：2019-01-01 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
pub_type： 杂志文章
doi：10.1007/s10822-016-0005-2
更新日期：2017-02-01 00:00:00
abstract：:A quantitative analysis of the interaction sites of the anti-Alzheimer drug galanthamine with molecular probes (water and benzene molecules) representative of its surroundings in the binding site of acetylcholinesterase (AChE) has been realized through pairwise potentials calculations and quantum chemistry. This strat...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9602-x
更新日期：2012-10-01 00:00:00
abstract：:Atomic-resolution structures of the transmembrane 7-alpha-helical domains of 26 G-protein-coupled receptors (GPCRs) (including opsins, cationic amine, melatonin, purine, chemokine, opioid, and glycoprotein hormone receptors and two related proteins, retinochrome and Duffy erythrocyte antigen) were calculated by distan...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章,评审
doi：10.1023/a:1008050821744
更新日期：1999-07-01 00:00:00
abstract：:The project on crystallographic modelling aims at extending the application of interactive graphics to inorganic structures. Starting from the available expertise in organic and protein modelling, the symmetry of the crystal structure is used not only to draw fixed models of many unit cells of the structure, which as ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF01531996
更新日期：1988-10-01 00:00:00
abstract：:A linear quantitative-structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Step...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-006-9038-2
更新日期：2006-02-01 00:00:00
abstract：:We examined "descriptor collision" for several chemical fingerprint systems (MDL 320, Daylight, SMDL), and for a 2D-based descriptor set. For large databases (ChemNavigator and WOMBAT), the smallest collision rate remains around 5%. We systematically increase the "descriptor collision" rate (here termed "descriptor co...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-9020-4
更新日期：2005-09-01 00:00:00
abstract：:The linear finite difference Poisson-Boltzmann (FDPB) equation is applied to the calculation of the electrostatic binding free energies of a group of inhibitors to the Neuraminidase enzyme. An ensemble of enzyme-inhibitor complex conformations was generated using Monte Carlo simulations and the electrostatic binding f...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008197913568
更新日期：2001-02-01 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
pub_type： 杂志文章
doi：10.1007/s10822-019-00249-1
更新日期：2020-02-01 00:00:00
abstract：:The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challeng...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-016-9946-8
更新日期：2016-09-01 00:00:00
abstract：:Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no or...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9807-2
更新日期：2015-01-01 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
pub_type： 杂志文章
doi：10.1007/s10822-016-9932-1
更新日期：2016-08-01 00:00:00
abstract：:Capacity ratio (log k') values, which are a measure of hydrophobicity, were calculated directly from the three-dimensional structures of 17 furans and 54 triazines using the comparative molecular field analysis approach. The H2O probe and the GRID force field, including hydrogen-bond potentials, yielded excellent corr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125172
更新日期：1995-08-01 00:00:00
abstract：:We employed a combination of molecular docking and dynamics to understand the interaction of three different radical scavengers (SB-HSC21, ABNM13 and trimidox) with ribonucleotide reductase M2 (hRRM2) domain. On the basis of the observed results, we can propose how these ligands interact with the enzyme, and cease the...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9581-y
更新日期：2012-07-01 00:00:00
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
pub_type： 杂志文章
doi：10.1007/BF00126748
更新日期：1994-06-01 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
pub_type： 杂志文章
doi：10.1007/s10822-020-00355-5
更新日期：2020-12-01 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
pub_type： 杂志文章
doi：10.1007/s10822-018-0105-2
更新日期：2018-04-01 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
pub_type： 杂志文章
doi：10.1007/s10822-020-00287-0
更新日期：2020-05-01 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
pub_type： 杂志文章
doi：10.1007/s10822-020-00342-w
更新日期：2020-10-05 00:00:00
abstract：:We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charge models in the context of explicit solvent free energy simulations with the general AMBER force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9714-6
更新日期：2014-03-01 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
pub_type： 杂志文章
doi：10.1007/s10822-011-9473-6
更新日期：2011-10-01 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
pub_type： 杂志文章
doi：10.1007/s10822-020-00356-4
更新日期：2020-10-26 00:00:00
abstract：:The pharmacophoric concept plays an important role in ligand-based drug design methods to describe the similarity and diversity of molecules, and could also be exploited as a molecular representation scheme. A three-point pharmacophore method was used as a molecular representation perception. This procedure was implem...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9110-6
更新日期：2007-05-01 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
pub_type： 杂志文章
doi：10.1007/s10822-012-9574-x
更新日期：2012-07-01 00:00:00
abstract：:A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates int...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124387
更新日期：1992-02-01 00:00:00
abstract：:A new and rigorous method for the fractional description of solvation and transfer free energies is presented. The method is based on the use of the Miertus-Scrocco-Tomasi self-consistent reaction field method (MST-SCRF), and allows for a rigorous partition of the total solvation free energy into surface elements. The...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008036526741
更新日期：1999-03-01 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
pub_type： 杂志文章
doi：10.1023/b:jcam.0000022559.72848.1c
更新日期：2004-01-01 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
pub_type： 杂志文章
doi：10.1007/s10822-017-0038-1
更新日期：2017-08-01 00:00:00
abstract：:Steric complementarity is a prerequisite for ligand-receptor recognition; this implies that drugs with a common receptor binding site should possess sterically similar binding surfaces. This principle is used as the basis for an automatic and unbiased method that superposes molecules. One molecule is rotated and trans...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124319
更新日期：1995-12-01 00:00:00
abstract：:The complex of adenylate kinase with its transition-state inhibitor has been studied by molecular dynamics simulations in water and in vacuum environments with the GROMOS force field over a period of 300 ps. The adenylate kinase, a member of the nucleotide-binding protein family, was exemplarily chosen for the inspect...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125373
更新日期：1994-08-01 00:00:00
