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：:Recent advances in algorithmic techniques and statistics of sequence alignment have helped to make near-optimal alignments an important tool in the delineation of biologically valid alignments. Near-optimal alignments serve to judge the reliability of portions of a sequence alignment. The statistical assessment of sub...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80054-6
更新日期：1996-06-01 00:00:00
abstract：:ATP synthases are rotary enzymes found in bacteria, chloroplasts, and mitochondria. These complexes produce the majority of cellular ATP in aerobic cells using energy from the transmembrane proton motive force established by the electron transport chain. In mitochondria, dimeric ATP synthase is essential for formation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.08.005
更新日期：2018-10-01 00:00:00
abstract：:Pore-forming proteins (PFPs), involved in host-pathogen interactions, are produced as soluble, generally monomeric, proteins. To convert from the soluble to the transmembrane form, PFPs assemble, in the vicinity of the target membrane, into ring-like structures, which expose sufficient hydrophobicity to drive spontane...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2010.01.013
更新日期：2010-04-01 00:00:00
abstract：:Structural modeling of a cell is an evolving strategic direction in computational structural biology. It takes advantage of new powerful modeling techniques, deeper understanding of fundamental principles of molecular structure and assembly, and rapid growth of the amount of structural data generated by experimental t...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.03.012
更新日期：2019-04-01 00:00:00
abstract：:Viruses with an icosahedrally symmetric protein capsid and a membrane infect hosts from all three domains of life. Similar architectural principles are shared by different viral families, as exemplified by double-stranded DNA viruses such as PRD1 and STIV. During virus assembly, the membrane lipids are selectively acq...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2007.03.005
更新日期：2007-04-01 00:00:00
abstract：:Progress in the synthesis, purification and crystallization of RNA has resulted in the determination of several X-ray crystal structures of RNA molecules over the past few years. Methods proven and under development will lead to future structure determinations and shed light on the structural basis for RNA's many func...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80057-3
更新日期：1995-10-01 00:00:00
abstract：:The bacterial cholesterol dependent cytolysins (CDCs) and membrane attack complex/perforin-like proteins (MACPF) represent two major branches of a large, exceptionally diverged superfamily. Most characterized CDC/MACPF proteins form large pores that function in immunity, venoms, and pathogenesis. Extensive structural,...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2012.04.008
更新日期：2012-06-01 00:00:00
abstract：:Current research into the morphology of lipid membranes focuses on three areas: first, the transformations and fluctuations of the shape of freely suspended vesicles; second, the morphology of membranes that experience mutual interactions or external forces arising, for example, from a macroscopic surface or from opti...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80040-9
更新日期：1995-08-01 00:00:00
abstract：:Protein design efforts are beginning to yield molecules with many of the properties of natural proteins. Such experiments are informed by and contribute to our understanding of the sequence determinants of protein folding and stability. The most important design elements seem to be the proper placement of hydrophobic ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(96)80088-1
更新日期：1996-02-01 00:00:00
abstract：:Asymmetric cell division (ACD) is a strategy for achieving cell diversity. Research carried out over the last two decades has shown that in some cell types that divide asymmetrically, mother and daughter centrosomes are noticeably different from one another in structure, behaviour, and fate, and that robust ACD depend...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.10.023
更新日期：2020-12-03 00:00:00
abstract：:Toll-like receptors (TLRs) activate the innate immune system in response to invading pathogens. Although nucleic acids are one of the principal TLR ligands, they are not inherently pathogen-specific and, thus, carry the risk of triggering autoimmunity. There are multiple unique regulatory mechanisms aimed at preventin...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.05.010
更新日期：2017-12-01 00:00:00
abstract：:Fucose is a common terminal modification on protein and lipid glycans. Fucose can also be directly linked to protein via an O-linkage to Serine or Threonine residues located within consensus sequences contained in Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs). In this context, fuc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.12.005
更新日期：2019-06-01 00:00:00
abstract：:Antibody engineering has been an extremely intensive research area for many years. Recent achievements discussed in this review include: (i) significant improvements in the field of selection of antigen-specific antibody fragments on bacteriophages; (ii) new structural work, in particular using NMR; (iii) the cloning ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80028-x
更新日期：1995-08-01 00:00:00
abstract：:Alternatively spliced protein segments tend to be intrinsically disordered and contain linear interaction motifs and/or post-translational modification sites. An emerging concept is that differential inclusion of such disordered segments can mediate new protein interactions, and hence change the context in which the b...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.03.006
更新日期：2013-06-01 00:00:00
abstract：:When a protein's function cannot be experimentally determined, it can often be inferred from sequence similarity. Should this process fail, analysis of the protein structure can provide functional clues or confirm tentative functional assignments inferred from the sequence. Many structure-based approaches exist (e.g. ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2005.04.003
更新日期：2005-06-01 00:00:00
abstract：:Magic-angle spinning solid-state NMR experiments are well suited to investigating the structures and mechanisms of important proteins that are inaccessible to X-ray crystallography and solution NMR spectroscopy, including membrane proteins and disease-related protein aggregates. Good progress has been made in the deve...
journal_title：Current opinion in structural biology
pub_type： 杂志文章
doi：10.1016/s0959-440x(02)00374-3
更新日期：2002-10-01 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：:Transition states in protein folding are being analyzed experimentally and by computer simulation to reveal the sequence of events in the folding and unfolding of proteins at high resolution. Results of this analysis have enabled the reconstruction of folding pathways in vitro and open the prospect of analyzing pathwa...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/0959-440x(95)80012-p
更新日期：1995-02-01 00:00:00
abstract：:The recently determined structure of octameric mitochondrial creatine kinase has provided new insights into the functioning of this enzyme and its role in channelling energy from the mitochondria to the cytoplasm. Creatine kinase, a member of the family of guanidino kinases, is structurally similar to glutamine synthe...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80151-0
更新日期：1997-12-01 00:00:00
abstract：:Recent studies from several laboratories have provided evidence that cell surface complex carbohydrates play key roles in the regulation of developmentally relevant signal transduction events. The demonstration that Fringe, a known modifier of Notch function, is a fucose-specific N-acetylglucosaminyltransferase provid...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00371-8
更新日期：2002-10-01 00:00:00
abstract：:The past years have seen tremendous progress towards understanding how arrestins recognize phosphorylated G protein-coupled receptors (GPCRs). Two arrestin crystal structures, one of a pre-activated splice variant and one bound to a GPCR phosphopeptide, provided insights into the conformational changes upon phosphate ...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.07.006
更新日期：2014-12-01 00:00:00
abstract：:Crystallographic studies of a number of aminoacyl-tRNA synthetases and their complexes with ATP, amino acid and cognate tRNA are leading to an increasingly detailed picture of how these sophisticated enzymes function. Within the two distinct structural classes of ten synthetases, many common features are apparent, alt...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(97)80161-3
更新日期：1997-12-01 00:00:00
abstract：:Specific interactions between proteins and their molecular partners drive most biological processes, so understanding how these interactions evolve is an important question for biochemists and evolutionary biologists alike. It is often thought that ancestral proteins were systematically more promiscuous than modern pr...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2017.07.003
更新日期：2017-12-01 00:00:00
abstract：:Intrinsically Disordered Proteins (IDPs) perform a broad range of biological functions. Their relevance has motivated intense research activity seeking to characterize their sequence/structure/function relationships. However, the conformational plasticity of these molecules hampers the application of traditional struc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.10.011
更新日期：2017-02-01 00:00:00
abstract：:Caspases are a family of aspartate-specific cysteine proteases that regulate cellular homeostasis through the mediation of apoptosis and inflammation. Despite keen interest in caspases as therapeutic targets for cancer, inflammatory, and neurodegenerative diseases, no active-site directed small molecule has yet succee...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.10.002
更新日期：2013-12-01 00:00:00
abstract：:Cyanobacteriochrome photoreceptors are linear tetrapyrrole-binding photoreceptors that are distantly related to the canonical phytochrome photoreceptors. The chromophore-binding region of the cyanobacteriochromes consists of only a cGMP-phosphodiesterase/adenylate cyclase/FhlA (GAF) domain, while that of the phytochro...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.01.018
更新日期：2019-08-01 00:00:00
abstract：:As a result of the recent enormous technological progress, experimental structure determination has become an integral part of the development of drugs against disease-related target proteins. The post-translational modification of proteins is an important regulatory process in living organisms; one such example is ly...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2006.10.014
更新日期：2006-12-01 00:00:00
abstract：:ATP-binding cassette (ABC) transporters are central to many physiological processes, including the uptake of nutrients, the non-classical secretion of signaling molecules and toxins, multidrug resistance and the development of human disease. As one might expect from this spectrum of translocation events, these ubiquit...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00399-8
更新日期：2002-12-01 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：: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
