Abstract：
:Computational protein design - the search for amino acids that adopt defined structures and functions - has achieved significant successes in recent years. Design is often approached from the perspective of targeting the design objective one structure-sequence pair at a time. Here we summarize studies that take an alternate approach, considering design solutions from the perspective of conformational and sequence ensembles. We argue that this strategy both more closely mimics the properties of naturally occurring proteins and drives progress in engineering. We discuss benchmarks for evaluating design methods, highlight recent advances, and project how the evolving capabilities of gene sequencing, gene synthesis, and genome editing may change the design field.
journal_name
Curr Opin Struct Bioljournal_title
Current opinion in structural biologyauthors
Friedland GD,Kortemme Tdoi
10.1016/j.sbi.2010.02.004subject
Has Abstractpub_date
2010-06-01 00:00:00pages
377-84issue
3eissn
0959-440Xissn
1879-033Xpii
S0959-440X(10)00037-0journal_volume
20pub_type
杂志文章,评审abstract：:Proteins are chief actors in life that perform a myriad of exquisite functions. This diversity has been enabled through the evolution and diversification of protein folds. Analysis of sequences and structures strongly suggest that numerous protein pieces have been reused as building blocks and propagated to many moder...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.12.007
更新日期：2021-01-13 00:00:00
abstract：:ATP-binding cassette (ABC)-type ATPases are chemo-mechanical engines for diverse biological pathways. ABC ATPase domains act not only in ABC transporters but also in DNA mismatch, nucleotide excision and double-strand break repair enzymes, as well as in chromosome segregation. Atomic-resolution crystal structures sugg...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(03)00037-x
更新日期：2003-04-01 00:00:00
abstract：:There are now numerous examples of proteins that are unstructured or only partially structured under physiological conditions and yet are nevertheless functional. Such proteins are especially prevalent in eukaryotes. In many cases, intrinsically disordered proteins adopt folded structures upon binding to their biologi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(02)00289-0
更新日期：2002-02-01 00:00:00
abstract：:Polyketide synthases (PKSs) form a large family of multifunctional proteins involved in the biosynthesis of diverse classes of natural products. Architecturally at least three different types of PKSs have been discovered in the microbial world and recent years have revealed tremendous versatility of PKSs, both in term...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2007.08.021
更新日期：2007-12-01 00:00:00
abstract：:A large body of work has gone into understanding the effect of mutations on protein structure and function. Conventional treatments have involved quantifying the change in stability, activity and relaxation rates of the mutants with respect to the wild-type protein. However, it is now becoming increasingly apparent th...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.09.004
更新日期：2019-02-01 00:00:00
abstract：:This review focuses on pharmacophore approaches in researching protein interfaces that bind protein ligands. Pharmacophore descriptions of binding interfaces that employ molecular dynamics simulation can account for effects of solvation and conformational flexibility. In addition, these calculations provide an approxi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.12.016
更新日期：2021-01-21 00:00:00
abstract：:Few biological macromolecular complexes exhibit the combination of massive size and hierarchical, symmetrical architecture embodied in icosahedral viruses. X-ray crystallography, electron cryomicroscopy and small-angle X-ray scattering provide complementary approaches to studying these remarkable structures. Through a...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2003.09.007
更新日期：2003-10-01 00:00:00
abstract：:Cohesin-Dockerin interactions are at the core of cellulosomal assembly and organization. They are highly specific and form stable complexes, allowing cellulosomes to adopt distinct conformations. Each cellulosomal system seems to have a particular organizational strategy that can vary in complexity according to the na...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2018.03.012
更新日期：2018-04-01 00:00:00
abstract：:Functional conformational changes of proteins can facilitate numerous biological events in cells. The Markov state model (MSM) built from molecular dynamics simulations provide a powerful approach to study them. We here introduce a protocol that is tailor-made for constructing MSMs to study the functional conformation...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.10.005
更新日期：2020-10-27 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：:Arf GTPases are major regulators of membrane traffic and organelle structure in eukaryotes where they recruit many different effectors, including components of vesicular coats, proteins that tether membranes, sort lipids or have diverse other functions in vesicular traffic, and bacterial proteins that divert Arf funct...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.09.007
更新日期：2014-12-01 00:00:00
abstract：:The amide bond with its planarity and lack of chemical reactivity is at the heart of protein structure. Chemical methylation of amides is known but was considered too harsh to be accessible to biology. Until last year there was no protein structure in the data bank with an enzymatically methylated amide. The discovery...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2020.06.004
更新日期：2020-12-01 00:00:00
abstract：:Fundamental biological processes are driven by diverse molecular machineries. In recent years, single-molecule fluorescence spectroscopy has matured as a unique tool in biology to study how structural dynamics of molecular complexes drive various biochemical reactions. In this review, we highlight underlying developme...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.005
更新日期：2019-10-01 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：:Peptide-mediated interactions are gaining increased attention due to their predominant roles in the many regulatory processes that involve dynamic interactions between proteins. The structures of such interactions provide an excellent starting point for their characterization and manipulation, and can provide leads fo...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2013.07.006
更新日期：2013-12-01 00:00:00
abstract：:Electron cryo-microscopy (cryoEM) is used to determine structures of biological molecules, including multi-protein complexes. Maps at better than 3.0Å resolution are relatively straightforward to interpret since atomic models of proteins and nucleic acids can be built directly. Still, these resolutions are often diffi...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.06.009
更新日期：2019-10-01 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：: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 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：:Condensation of DNA in the nucleosome takes advantage of its double-helical architecture. The DNA deforms at sites where the base pairs face the histone octamer. The largest so-called kink-and-slide deformations occur in the vicinity of arginines that penetrate the minor groove. Nucleosome structures formed from the 6...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2011.03.006
更新日期：2011-06-01 00:00:00
abstract：:Specific, noncovalent binding of biomolecules can only be understood by considering structural, thermodynamic, and kinetic issues. The theoretical foundations for such analyses have been clarified in the past year. Computational techniques for both particle-based and continuum models continue to improve and to yield u...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80046-8
更新日期：1998-04-01 00:00:00
abstract：:Advances in electron microscopes, detectors and data processing algorithms have greatly facilitated the structural determination of many challenging integral membrane proteins that have been evasive to crystallization. These breakthroughs facilitate the application and development of various membrane protein solubiliz...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.05.022
更新日期：2019-10-01 00:00:00
abstract：:Intermediate filaments are built from one to several members of a multigene family encoding fibrous proteins that share a highly conserved hierarchic assembly plan for the formation of multistranded filaments from distinctly structured extended coiled coils. Despite the rather low primary sequence identity, intermedia...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(98)80035-3
更新日期：1998-04-01 00:00:00
abstract：:Investigating the in vitro refolding of proteins that naturally reside in biological membranes is a notoriously difficult task. Biophysical studies on model systems are beginning to provide a sound physical basis for membrane protein folding that should help to alleviate this problem. Highlights of these studies inclu...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/s0959-440x(99)80015-3
更新日期：1999-02-01 00:00:00
abstract：:Mechanisms for making and breaking the heme b cofactor (heme) are more diverse than previously expected. Biosynthetic pathways have diverged at least twice along taxonomic lines, reflecting differences in membrane organization and O2 utilization among major groups of organisms. At least three families of heme degradas...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2019.01.006
更新日期：2019-12-01 00:00:00
abstract：:Glycosylation is a common post-translational protein modification, in which glycans are built onto proteins through the sequential addition of monosaccharide units, in reactions catalysed by glycosyltransferases. Glycosylation influences the physicochemical and biological properties of proteins, with subsequent effect...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.08.007
更新日期：2016-10-01 00:00:00
abstract：:ATP- and NAD(+)-dependent DNA ligases, ATP-dependent RNA ligases and GTP-dependent mRNA capping enzymes comprise a superfamily of proteins that catalyze nucleotidyl transfer to polynucleotide 5' ends via covalent enzyme-(lysyl-N)-NMP intermediates. The superfamily is defined by five peptide motifs that line the nucleo...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2004.10.006
更新日期：2004-12-01 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：:All domains of life make carbohydrate polymers and by anchoring them to lipid molecules they can decorate the outside of the cell. Polysaccharides are linked to proteins by glycosylation, a process found in both bacteria and in higher organisms. Bacteria do have other distinct uses for carbohydrate polymers; in gram-n...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2016.07.016
更新日期：2016-10-01 00:00:00
abstract：:Generally, non-catalytic carbohydrate binding module (CBM) specificity has been shown to parallel the catalytic activity of the carbohydrate active enzyme (CAZyme) module it is appended to. With the rapid expansion in metagenomic sequence space for the potential discovery of new CBMs in addition to the recent emergenc...
journal_title：Current opinion in structural biology
pub_type： 杂志文章,评审
doi：10.1016/j.sbi.2014.07.004
更新日期：2014-10-01 00:00:00
