Abstract：
:Improved rational drug design methods are needed to lower the cost and increase the success rate of drug discovery and development. Alchemical binding free energy calculations, one potential tool for rational design, have progressed rapidly over the past decade, but still fall short of providing robust tools for pharmaceutical engineering. Recent studies, especially on model receptor systems, have clarified many of the challenges that must be overcome for robust predictions of binding affinity to be useful in rational design. In this review, inspired by a recent joint academic/industry meeting organized by the authors, we discuss these challenges and suggest a number of promising approaches for overcoming them.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Chodera JD,Mobley DL,Shirts MR,Dixon RW,Branson K,Pande VSdoi
10.1016/j.sbi.2011.01.011subject
Has Abstractpub_date
2011-04-01 00:00:00pages
150-60issue
2eissn
0959-440Xissn
1879-033Xpii
S0959-440X(11)00026-1journal_volume
21pub_type
杂志文章,评审abstract：:Eukaryotic transcriptional coactivators are multi-subunit complexes that both modify chromatin and recognize histone modifications. Until recently, structural information on these large complexes has been limited to isolated enzymatic domains or chromatin-binding motifs. This review summarizes recent structural studie...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.09.004
更新日期：2011-12-01 00:00:00
abstract：:Carbohydrate microarray technologies are new developments at the frontiers of glycomics. Results of 'proof of concept' experiments with carbohydrate-binding proteins of the immune system - antibodies, selectins, a cytokine and a chemokine - and several plant lectins indicate that microarrays of carbohydrates (glycocon...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2003.09.002
更新日期：2003-10-01 00:00:00
abstract：:Demand for novel GPCR modulators is increasing as the association between the GPCR signaling pathway and numerous diseases such as cancers, psychological and metabolic disorders continues to be established. In silico structure-based drug design (SBDD) offers an outlet where researchers could exploit the accumulating s...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.03.015
更新日期：2019-04-01 00:00:00
abstract：:The past year has witnessed a tremendous increase in our understanding of the structures and interactions of the GTPases. The highlights include crystal structures of G alpha subunits, as well as the first complex between a GTPase (Rap1A) and an effector molecule (c-Raf1 Ras-binding domain). In the field of elongation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80015-8
更新日期：1995-12-01 00:00:00
abstract：:Biology can teach the physical world of electronics, computing, materials science and manufacturing how to assemble complex functional devices and systems that operate at the molecular level. Our present capability to fabricate simple molecular tools, devices, materials and machines is primitive compared with the soph...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(00)00110-x
更新日期：2000-08-01 00:00:00
abstract：:Recent advances in neutron and X-ray sources and instrumentation, new and improved scattering techniques, and molecular biology techniques, which have permitted facile preparation of samples, have each led to new opportunities in using small-angle scattering to study the conformations and interactions of biological ma...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80081-4
更新日期：1997-10-01 00:00:00
abstract：:NMR relaxation experiments of isotopically labeled proteins provide a wealth of information on reorientational global and local dynamics on nanosecond and subnanosecond timescales for folded and nonfolded proteins in solution. Recent methodological advances in the interpretation of relaxation data have led to a better...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(03)00036-8
更新日期：2003-04-01 00:00:00
abstract：:Integrative structural modeling uses multiple types of input information and proceeds in four stages: (i) gathering information, (ii) designing model representation and converting information into a scoring function, (iii) sampling good-scoring models, and (iv) analyzing models and information. In the first stage, unc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.08.001
更新日期：2014-10-01 00:00:00
abstract：:ATP-dependent initiation factors help process replication origins and coordinate replisome assembly to control the onset of DNA synthesis. Although the specific properties and regulatory mechanisms of initiator proteins can vary greatly between different organisms, certain nucleotide-binding elements and assembly patt...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2012.11.012
更新日期：2013-02-01 00:00:00
abstract：:Recent advances in atomic force microscopy (AFM) imaging of nucleic acids include the visualization of DNA and RNA incorporated into devices and patterns, and into structures based on their sequences or sequence recognition. AFM imaging of nuclear structures has contributed to advances in telomere research and to our ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.05.005
更新日期：2004-06-01 00:00:00
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 d...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.06.022
更新日期：2020-10-01 00:00:00
abstract：:The structure of tubulin has recently been determined by electron crystallography, paving the way for a clearer understanding of the unique properties of tubulin that allow its varied functions within the cell. Some of the ongoing work on tubulin can be interpreted in terms of its structure, which can serve to guide f...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80099-7
更新日期：1998-12-01 00:00:00
abstract：:Directed evolution is widely used to improve enzymes, particularly for industrial biocatalytic processes. Molecular biology advances present many new strategies for directed evolution. Commonly used techniques have led to many successful examples of enzyme improvement, yet there is still a need to improve both the eff...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.05.003
更新日期：2011-08-01 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：:The past decade has witnessed the development of numerous systems for the presentation of antigens on the surface of self-assembling macromolecules. Although the sites for insertion were initially chosen empirically, the determination of the three-dimensional structures of a number of carrier macromolecules has enable...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80072-8
更新日期：1996-04-01 00:00:00
abstract：:The accelerated elucidation of three-dimensional structures of protein complexes, both natural and designed, is providing new examples of large supramolecular assemblies with intriguing shapes. Those with high symmetry - based on the geometries of the Platonic solids - are particularly notable as their innately closed...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.03.008
更新日期：2019-04-01 00:00:00
abstract：:There has been significant recent progress in the computational design of protein interactions including the creation of novel heterodimers, homodimers, nanohedra, fibril caps and a protein crystal. Essential to these successes has been the use of innovative strategies for finding binding modes that are achievable, th...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.04.010
更新日期：2013-08-01 00:00:00
abstract：:The computational evaluation of protein-protein interactions will play an important role in organising the wealth of data being generated by high-throughput initiatives. Here we discuss future applications, report recent developments and identify areas requiring further investigation. Many functions have been develope...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.06.017
更新日期：2013-12-01 00:00:00
abstract：:Terpenoid cyclases catalyze remarkably complex cyclization cascades that are initiated by the formation of a highly reactive carbocation in a polyisoprene substrate. Recent crystal structures of terpenoid cyclases show how these enzymes provide a template for binding and stabilizing the flexible substrate in the preci...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80088-2
更新日期：1998-12-01 00:00:00
abstract：:Connecting three dimensional structure and affinity is analogous to seeking the 'Archimedean point', a vantage point from where any observer can quantitatively perceive the subject of inquiry. Here we review current knowledge and challenges that lie ahead of us in the quest for this Archimedean point. We argue that cu...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.07.001
更新日期：2013-12-01 00:00:00
abstract：:The RNA exosome participates in the degradation and processing of a wide range of RNA molecules. Recent advances in understanding how the exosome is organized and functions largely stem from structural studies. Crystal structures of archaeal exosomes bound to RNA and of the corresponding nine-subunit human exosome cor...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2008.10.004
更新日期：2008-12-01 00:00:00
abstract：:The base pair stack within double helical DNA provides an effective medium for charge transport. The DNA pi-stack mediates oxidative DNA damage over long molecular distances in a reaction that is exquisitely sensitive to the sequence-dependent conformation and dynamics of DNA. A mixture of tunneling and hopping mechan...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00327-5
更新日期：2002-06-01 00:00:00
abstract：:Over recent years, nuclear magnetic resonance (NMR) spectroscopy has developed into a powerful mechanistic tool for the investigation of G protein-coupled receptors (GPCRs). NMR provides insights which underpin the dynamic nature of these important receptors and reveals experimental evidence for a complex conformation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.03.030
更新日期：2019-08-01 00:00:00
abstract：:The past two years have seen the extension of our knowledge on the cellular prion protein structure with new NMR data on both the hamster and human proteins. In addition, the folding dynamics of two cellular prion proteins have been elucidated. There are now several examples of recombinant prion proteins that are able...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)00051-2
更新日期：2000-02-01 00:00:00
abstract：:Covalent modifications of histone proteins regulate a wide variety of cellular processes. Methylation of histone H3K79 and H3K4 is associated with active transcription and is catalyzed by Dot1L and Set1, respectively. Both Dot1L and Set1 are activated by prior ubiquitination of histone H2B on K120 in a process termed ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.009
更新日期：2019-12-01 00:00:00
abstract：:Glycoproteins and protein-carbohydrate complexes in the worldwide Protein Data Bank (wwPDB) can be an excellent source of information for glycoscientists. Unfortunately, a rather large number of errors and inconsistencies is found in the glycan moieties of these 3D structures. This review illustrates frequent problems...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.10.010
更新日期：2017-06-01 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：:A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Structural Biology. ...
journal_title：Current opinion in structural biology
pub_type：
doi：10.1016/s0959-440x(00)00182-2
更新日期：2001-04-01 00:00:00
abstract：:Pyrrolopyrimidine containing natural products are widely distributed in Nature. The biosynthesis of the 7-deazapurine moiety that is common to all pyrrolopyrimidines entails multiple steps, one of which is a complex radical-mediated ring contraction reaction catalyzed by CDG synthase. Herein we review the biosynthetic...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2015.11.005
更新日期：2015-12-01 00:00:00
abstract：:Intrinsically disordered proteins (IDPs) are increasingly realized to play diverse biological roles, ranging from molecular signaling to the formation of membraneless organelles. Their high degree of disorder makes them more challenging to study using the techniques of conventional structural biology, because any obse...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.01.006
更新日期：2017-02-01 00:00:00
