Abstract：
:Due to the contribution of drug-target binding kinetics to drug efficacy, there is a high level of interest in developing methods to predict drug-target binding kinetic parameters. During the review period, a wide range of enhanced sampling molecular dynamics simulation-based methods has been developed for computing drug-target binding kinetics and studying binding and unbinding mechanisms. Here, we assess the performance of these methods considering two benchmark systems in detail: mutant T4 lysozyme-ligand complexes and a large set of N-HSP90-inhibitor complexes. The results indicate that some of the simulation methods can already be usefully applied in drug discovery or lead optimization programs but that further studies on more high-quality experimental benchmark datasets are necessary to improve and validate computational methods.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Nunes-Alves A,Kokh DB,Wade RCdoi
10.1016/j.sbi.2020.06.022subject
Has Abstractpub_date
2020-10-01 00:00:00pages
126-133eissn
0959-440Xissn
1879-033Xpii
S0959-440X(20)30121-4journal_volume
64pub_type
杂志文章,评审abstract：:The ribosome undergoes numerous large-scale conformational changes during protein synthesis, but the molecular basis for these changes have been unclear. Recent cryo-electron microscopic and X-ray crystallographic structures of both the bacterial and eukaryotic ribosome now provide snapshots of the wide range of motio...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2012.07.011
更新日期：2012-12-01 00:00:00
abstract：:Translation initiation in eukaryotes is a complex multistep process that requires the interplay of over a dozen protein factors together with the small ribosomal subunit (SSU) and the mRNA. During all these steps, the SSU serves as a platform for attachment, displacement and release of different molecules. In recent y...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.08.006
更新日期：2018-12-01 00:00:00
abstract：:The wide occurrence of sialic acids (Sia) in various chemical forms linked as monomers or polymers in an outstanding position in a multitude of complex carbohydrates of animals and microorganisms renders them as most versatile function modulators in cell biology and pathology. A survey is presented of recent advances ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.06.003
更新日期：2009-10-01 00:00:00
abstract：:The structure of the visual pigment rhodopsin in the dark state was first investigated by electron microscopy (EM). More recently, rhodopsin has been crystallised in two different space groups--a tetragonal P4(1) crystal form and a trigonal P3(1) packing arrangement. The structures of the pigment, determined by X-ray ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.07.010
更新日期：2005-08-01 00:00:00
abstract：:The 26S proteasome is the essential compartmental protease in eukaryotic cells required for the ubiquitin-dependent clearance of damaged polypeptides and obsolete regulatory proteins. Recently, a combination of high-resolution structural, biochemical, and biophysical studies has provided crucial new insights into the ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.10.004
更新日期：2020-04-01 00:00:00
abstract：:The sema domain was first defined from sequence by Kolodkin and colleagues in the early 1990s, and constitutes the distinctive structural and functional element of semaphorins, their plexin receptors and the receptor tyrosine kinases MET and RON, three protein families with major roles in development, tissue regenerat...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.10.010
更新日期：2004-12-01 00:00:00
abstract：:Intrinsically disordered regions (IDRs) are fundamental units of protein function and regulation. Despite their inability to form a unique stable tertiary structure in isolation, many IDRs adopt a defined conformation upon binding and achieve their function through their interactions with other biomolecules. However, ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.05.007
更新日期：2014-06-01 00:00:00
abstract：:RNA-dependent RNA polymerases (RdRPs) play central roles in both transcription and viral genome replication. In picornaviruses, these functions are catalyzed by the virally encoded RdRP, termed 3D. Polymerase 3D also catalyzes the covalent linkage of UMP to a tyrosine on the small protein VPg. Uridylylated VPg then se...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.10.016
更新日期：2009-12-01 00:00:00
abstract：:An important goal of structural genomics is to complete the structural analysis of all the enzymes in metabolic pathways and to understand the structural similarities and differences. A preliminary glimpse of this type of analysis was achieved before structural genomics efforts with the glycolytic pathway and efforts ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00154-8
更新日期：2000-12-01 00:00:00
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journal_title：Current opinion in structural biology
pub_type： 杂志文章
doi：10.1016/s0959-440x(03)00101-5
更新日期：2003-08-01 00:00:00
abstract：:If protein structure prediction methods are to make any impact on the impending onerous task of analyzing the large numbers of unknown protein sequences generated by the ongoing genome-sequencing projects, it is vital that they make the difficult transition from computational 'gedankenexperiments' to practical softwar...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80055-3
更新日期：1997-06-01 00:00:00
abstract：:Channel-forming bacterial toxins undergo a series of remarkable changes in solubility, oligomerization state, structure and dynamics during the processes of membrane binding, assembly, membrane insertion and channel formation. Recent high-resolution crystal structures of channel-forming toxins, in both water-soluble a...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80123-6
更新日期：1997-08-01 00:00:00
abstract：:A remarkable group of proteins challenge the notions that protein sequence determines a unique three-dimensional structure, and that membrane and soluble proteins are very distinct. The pore-forming toxins typically transform from soluble, monomeric proteins to oligomers that form transmembrane channels. Recent struct...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.03.008
更新日期：2006-04-01 00:00:00
abstract：:Optogenetic dimerizers are modular domains that can be utilized in a variety of versatile ways to modulate cellular biochemistry. Because of their modularity, many applications using these tools can be easily transferred to new targets without extensive engineering. While a number of photodimerizer systems are current...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.01.021
更新日期：2019-08-01 00:00:00
abstract：:As the fundamental packing units of DNA in eukaryotes, nucleosomes play a central role in governing DNA accessibility in a variety of cellular processes. Our understanding of the mechanisms underlying this complex regulation has been aided by unique structural and dynamic perspectives offered by single molecule techni...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.11.003
更新日期：2012-02-01 00:00:00
abstract：:Eukaryotes possess a variety of translational control mechanisms which function in the surveillance of mRNAs, discriminating between normal and aberrant translation elongation and termination, triggering mRNA decay. The three major evolutionarily conserved eukaryotic pathways are No-Go, Non-Stop and Nonsense-Mediated ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.06.011
更新日期：2020-12-01 00:00:00
abstract：:Protein engineering strategies for increasing stability can be improved by replacing random mutagenesis and high-throughput screening by approaches that include bioinformatics and computational design. Mutations can be focused on regions in the structure that are most flexible and involved in the early steps of therma...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.04.008
更新日期：2013-08-01 00:00:00
abstract：:Malaria remains the world's most prevalent human parasitic disease. Because of the rapid spread of drug resistance in parasites, there is an urgent need to identify diverse new drug targets. One group of proteases that are emerging as targets for novel antimalarials are the metalloaminopeptidases. These enzymes cataly...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.07.015
更新日期：2013-12-01 00:00:00
abstract：:The X-ray structures of two prokaryotic pentameric ligand-gated ion channels have recently provided detailed insight into this important family of neurotransmitter receptors. These prokaryotic homologs share the overall architecture of their eukaryotic counterparts with conservation in functionally important residues....
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.07.006
更新日期：2009-08-01 00:00:00
abstract：:Understanding the structural rules that govern specific, high-affinity binding characteristic of aptamer-protein interactions is important in view of the increasing use of aptamers across many applications. From the modest number of 16 aptamer-protein structures currently available, trends are emerging. The flexible p...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.01.009
更新日期：2016-02-01 00:00:00
abstract：:This review emphasizes the effects of naturally occurring mutations on structural features and physico-chemical properties of proteins. The basic protein characteristics considered are stability, dynamics, and the binding of proteins and methods for assessing effects of mutations on these macromolecular characteristic...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.01.003
更新日期：2015-06-01 00:00:00
abstract：:Molecular flexibility over a wide time range is of central importance to the function of many proteins, both soluble and membrane. Revealing the modes of flexibility, their amplitudes, and time scales under physiological conditions is the challenge for spectroscopic methods, one of which is site-directed spin labeling...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.06.008
更新日期：2013-10-01 00:00:00
abstract：:Molecular dynamics simulations allow for atomic-level characterization of biomolecular processes such as the conformational transitions associated with protein function. The computational demands of such simulations, however, have historically prevented them from reaching the microsecond and greater timescales on whic...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.03.004
更新日期：2009-04-01 00:00:00
abstract：:Intron splicing is a fundamental biological process whereby noncoding sequences are removed from precursor RNAs. Recent work has provided new insights into the structural features and reaction mechanisms of two introns that catalyze their own splicing from precursor RNA: the group I and II introns. In addition, there ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2009.04.002
更新日期：2009-06-01 00:00:00
abstract：:Conformational dynamics is a hallmark of diverse non-coding RNA functions. During these functional processes, RNA molecules almost ubiquitously undergo conformational transitions that are tuned to meet distinct structural and kinetic requirements for proper function. A complete mechanistic understanding of RNA functio...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.02.011
更新日期：2015-02-01 00:00:00
abstract：:A network of dynamic protein interactions with their protein partners, substrates, and ligands is known to be crucial for biological function. Revealing molecular and structural-based mechanisms at atomic resolution and in real-time is fundamental for achieving a basic understanding of cellular processes. These techni...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.07.008
更新日期：2011-10-01 00:00:00
abstract：:Ribonuclease P (RNase P) is one of only two known universal ribozymes and was one of the first ribozymes to be discovered. It is involved in RNA processing, in particular the 5' maturation of tRNA. Unlike most other natural ribozymes, it recognizes and cleaves its substrate in trans. RNase P is a ribonucleoprotein com...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.04.002
更新日期：2006-06-01 00:00:00
abstract：:The ISWI family of ATP-dependent chromatin remodelers regulates transcription of coding and noncoding RNA by mobilizing nucleosomes and controlling the length of linker DNA separating nucleosomes (spacing). Nucleosome movement is tightly coupled to the DNA translocation activity of the helicase domain in the catalytic...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.01.010
更新日期：2014-02-01 00:00:00
abstract：:Recently solved structures and proposed models have helped to reveal the structural characteristics of the beta-propeller fold, as well as the features that contribute to its high rigidity and stability. Possible strategies for identifying beta-propeller proteins in newly characterised sequences are helping to overcom...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)00035-4
更新日期：1999-12-01 00:00:00
abstract：:Recently, atomic models of the mammalian, fungal and the bacterial fatty acid synthases type I (FAS I) were reported. Now, a wealth of functional data, collected during the last decades, can be embedded into structural frames. But there is more, which remains to be done! Our current considerations are implicitly very ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.12.004
更新日期：2014-04-01 00:00:00
