Empirical free energy as a target function in docking and design: application to HIV-1 protease inhibitors.

Abstract:

:Structure-based drug design requires the development of efficient computer programs for exploring the structural compatibility of various flexible ligands with a given receptor. While various algorithms are available for finding docked conformations, selecting a target function that can reliably score the conformations remains a serious problem. We show that the use of an empirical free energy evaluation method, originally developed to characterize protein-protein interactions, can substantially improve the efficacy of search algorithms. In addition to the molecular mechanics interaction energy, the function takes account of solvation and side chain conformational entropy, while remaining simple enough to replace the incomplete target functions used in many drug docking and design procedures. The free energy function is used here in conjunction with a simple site mapping-fragment assembly algorithm, for docking the MVT-101 non-peptide inhibitor to HIV-1 protease. In particular, we predict the bound structure with an all atom RMSD of 1.21 A, compared to 1.69 A using an energy target function, and also accurately predict the free energy shifts obtained with a series of five trimeric hydroxyethylene isostere analogs.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

King BL,Vajda S,DeLisi C

doi

10.1016/0014-5793(96)00276-1

subject

Has Abstract

pub_date

1996-04-08 00:00:00

pages

87-91

issue

1

eissn

0014-5793

issn

1873-3468

pii

0014-5793(96)00276-1

journal_volume

384

pub_type

杂志文章
  • S100A1 modulates skeletal muscle contraction by desensitizing calcium activation of isometric tension, stiffness and ATPase.

    abstract::S100, a subfamily of the EF-hand type calcium sensing proteins, is implicated in many cellular functions including muscle contractility. Two isoforms, S100A1 and S100B, at 2-10 microM significantly inhibit active tension, stiffness and ATPase of skinned single rabbit psoas muscle fibers at sub-maximal (pCa approximate...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(01)02444-9

    authors: Adhikari BB,Wang K

    更新日期:2001-05-25 00:00:00

  • A synthetic beta-casein phosphopeptide and analogues as model substrates for casein kinase-1, a ubiquitous, phosphate directed protein kinase.

    abstract::The phosphopeptide Ser (P)-Ser(P)-Ser-(P)-Glu-Glu-Ser22-Ile-Thr, reproducing the 17-24 segment of beta-casein A2 including the seryl residue (Ser-22) which is targeted by casein kinase-1 was synthesized and used as model substrate for this enzyme. Its phosphorylation efficiency is actually higher than that of intact b...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(91)80614-9

    authors: Meggio F,Perich JW,Reynolds EC,Pinna LA

    更新日期:1991-06-03 00:00:00

  • The pro sequence of lactase-phlorizin hydrolase is required for the enzyme to reach the plasma membrane. An intramolecular chaperone?

    abstract::Various cDNAs coding for part or all of human pre-pro lactase-phlorizin hydrolase (pre-proLPH) were transfected into COS cells and the subcellular location of the lactase-related proteins assessed. Only the complete proLPH reached the plasma membrane. LPH without the pro sequence, and a construct containing the pro se...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(93)80389-c

    authors: Oberholzer T,Mantei N,Semenza G

    更新日期:1993-10-25 00:00:00

  • Lipid droplets: a dynamic organelle moves into focus.

    abstract::Lipid droplets (LDs) were perceived as static storage deposits, which passively participate in the energy homeostasis of both cells and entire organisms. However, this view has changed recently after the realization of a complex and highly dynamic LD proteome. The proteome contains key components of the fat mobilizati...

    journal_title:FEBS letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.febslet.2010.03.022

    authors: Beller M,Thiel K,Thul PJ,Jäckle H

    更新日期:2010-06-03 00:00:00

  • Raf-1 is activated by the p38 mitogen-activated protein kinase inhibitor, SB203580.

    abstract::SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imi dazole) is widely used as a specific inhibitor of p38 mitogen-activated protein kinase (MAPK). Here, we report that SB203580 activates the serine/threonine kinase Raf-1 in quiescent smooth muscle cells in a dose-dependent fashion. The concentr...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(99)00034-4

    authors: Kalmes A,Deou J,Clowes AW,Daum G

    更新日期:1999-02-05 00:00:00

  • The glucagon-like peptide-1 receptor binding site for the N-terminus of GLP-1 requires polarity at Asp198 rather than negative charge.

    abstract::The mutation of Asp198 to Asn in the receptor for glucagon-like peptide-1(7-36)amide (GLP-1) had no effect upon GLP-1 affinity whereas substitution with Ala greatly reduced affinity, demonstrating the importance of polarity rather than negative charge at Asp198. However, the Asp198-Ala mutation had less effect upon th...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(02)03492-0

    authors: López de Maturana R,Donnelly D

    更新日期:2002-10-23 00:00:00

  • Saturable [D-Ala2, D-Leu5]-enkephalin transport into cholinergic synaptic vesicles.

    abstract::Incubation of cholinergic synaptic vesicles purified from the electric organ of Torpedo ocellata with radiolabeled [D-Ala2, D-Leu5]-enkephalin results in its accumulation in the vesicles. Kinetic analysis of the initial rates of uptake reveals temperature-dependent saturation kinetics which are best fitted by a single...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(85)80946-7

    authors: Day NC,Wien D,Michaelson DM

    更新日期:1985-04-08 00:00:00

  • In vitro synthesis, tetramerization and single channel characterization of virus-encoded potassium channel Kcv.

    abstract::Chlorella virus-encoded membrane protein Kcv represents a new class of potassium channel. This 94-amino acids miniature K(+) channel consists of two trans-membrane alpha-helix domains intermediated by a pore domain that contains a highly conserved K(+) selectivity filter. Therefore, as an archetypal K(+) channel, the ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2007.02.005

    authors: Shim JW,Yang M,Gu LQ

    更新日期:2007-03-06 00:00:00

  • Aminoacyl-coenzyme A synthesis catalyzed by a CoA ligase from Penicillium chrysogenum.

    abstract::Coenzyme A ligases play an important role in metabolism by catalyzing the activation of carboxylic acids. In this study we describe the synthesis of aminoacyl-coenzyme As (CoAs) catalyzed by a CoA ligase from Penicillium chrysogenum. The enzyme accepted medium-chain length fatty acids as the best substrates, but the p...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2011.02.018

    authors: Koetsier MJ,Jekel PA,Wijma HJ,Bovenberg RA,Janssen DB

    更新日期:2011-03-23 00:00:00

  • Protein syntheis in brain mitochondrial and synaptosomal preparations.

    abstract::The anomolous protein synthesis, sensitive to cycloheximide, which has been observed in brain mitochondrial and synaptosomal preparations, has been studied. It is concluded that this protein synthesis is due to the presence, as a contaminant in both preparations, of a ribosome-containing particle which contains solubl...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(70)80646-9

    authors: Morgan IG

    更新日期:1970-10-16 00:00:00

  • Mitochondrial membrane potential monitored in situ within isolated guinea pig brown adipocytes by a styryl pyridinium fluorescent indicator.

    abstract::2-( Dimethylaminostyryl )-l-methyl pyridinium, a fluorescent indicator of mitochondrial membrane potential, is accumulated up to 400-fold by intact, isolated brown adipocytes from cold-adapted guinea pigs. The indicator can be optically localized within the in situ mitochondria. Ionophores which would be predicted to ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(84)81395-2

    authors: Rafael J,Nicholls DG

    更新日期:1984-05-07 00:00:00

  • Structural and SAXS analysis of the budding yeast SHU-complex proteins.

    abstract::In Saccharomyces cerevisiae, four proteins, Shu1, Shu2, Psy3 and Csm2, form a stable SHU-complex both in vivo and in vitro. These proteins are involved in the early stages of the homologous recombination DNA damage repair process. In this paper, the crystal structure of the Psy3-Csm2 sub-complex is presented at 1.8Å r...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2012.06.024

    authors: She Z,Gao ZQ,Liu Y,Wang WJ,Liu GF,Shtykova EV,Xu JH,Dong YH

    更新日期:2012-07-30 00:00:00

  • Searching for the mechanism of signalling by plant photoreceptor cryptochrome.

    abstract::Even though the plant photoreceptors cryptochromes were discovered more than 20 years ago, the mechanism through which they transduce light signals to their partner molecules such as COP1 (Constitutive Photomorphogenic 1) or SPA1 (Suppressor of Phytochrome A) still remains to be established. We propose that a negative...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2014.12.008

    authors: Müller P,Bouly JP

    更新日期:2015-01-16 00:00:00

  • hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells.

    abstract::In Drosophila, the tumor suppressor Scribble is localized at the septate junctions of epithelial cells. Its mammalian homologue, hScrib, is a basolateral protein likely associated to proteins of the cell-cell junctions. We report the direct interaction between hScrib and ZO-2, a junction-associated protein. This inter...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2005.05.062

    authors: Métais JY,Navarro C,Santoni MJ,Audebert S,Borg JP

    更新日期:2005-07-04 00:00:00

  • Flanking aromatic residue competition influences transmembrane peptide helix dynamics.

    abstract::To address biophysical principles and lipid interactions that underlie the properties of membrane proteins, modifications that vary the neighbors of tryptophan residues in the highly dynamic transmembrane helix of GW4,20 ALP23 (acetyl-GGAW4 A(LA)6 LAW20 AGA-amide) were examined using deuterium NMR spectroscopy. It was...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1002/1873-3468.13926

    authors: McKay MJ,Greathouse DV,Koeppe RE 2nd

    更新日期:2020-12-01 00:00:00

  • Involvement of soluble proteinous factors in auxin-induced modulation of P-type ATPase in rice (Oryza sativa L.) seedlings.

    abstract::The marked difference in auxin sensitivity between plant roots and shoots was studied in terms of auxin-induced stimulation of membrane P-type ATPase. The results suggest the existence in rice seedlings of, at least, two isoforms of soluble proteinous factors (SPF), SPF(I) and SPF(II), which are involved in the stimul...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(97)00527-9

    authors: Kim D,Kim YS,Jung J

    更新日期:1997-06-09 00:00:00

  • Structure of DNA in metaphase chromosomes of mouse fibroblasts.

    abstract::We show that N-1 in adenine of chromosomal DNA is methylated by treatment of metaphase chromosomes with dimethylsulphate while this is not the case in chromatin. The data on methylation are consistent with those obtained from the experiments with S1-nuclease treatment of chromatin and chromosomes. This suggests a disa...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(83)80167-7

    authors: Belyaev ND,Budker VG,Dubrovskaya VA,Matveeva NM

    更新日期:1983-04-18 00:00:00

  • The complete primary structure of three isoforms of a boar sperm-associated acrosin inhibitor.

    abstract::Acrosin inhibitors of seminal vesicle origin, after binding to their acceptor molecules on the anterior part of ejaculated sperm, are thought to be important capacitation factors, protecting zona binding sites during sperm uterine passage, and then dissociating to allow sperm binding to the zona pellucida of the oocyt...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(92)80347-j

    authors: Jonáková V,Calvete JJ,Mann K,Schäfer W,Schmid ER,Töpfer-Petersen E

    更新日期:1992-02-03 00:00:00

  • The microtubule associated protein syntabulin is required for glucose-stimulated and cAMP-potentiated insulin secretion.

    abstract::Syntabulin is a microtubule-associated protein that mediates anterograde transport of vesicles to neuronal processes. Here, we found that syntabulin was expressed in mouse pancreas and insulin-secreting β-cells, and that it partially co-localized with microtubule and insulin-containing granules. The association of syn...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2012.08.025

    authors: Ying Y,Li L,Cao W,Yan D,Zeng Q,Kong X,Lu L,Yan M,Xu X,Qu J,Su Q,Ma X

    更新日期:2012-10-19 00:00:00

  • Occurrence of heme O in photoheterotrophically growing, semi-anaerobic cyanobacterium Synechocystis sp. PCC6803.

    abstract::Extraction and identification of the non-covalently bound heme groups from crude membrane preparations of photoheterotrophically grown Synechocystis sp. PCC 6803 by reversed phase high performance liquid chromatography and optical spectrophotometry led to the detection of heme O in addition to hemes B and A which latt...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(95)00821-p

    authors: Peschek GA,Wastyn M,Fromwald S,Mayer B

    更新日期:1995-09-04 00:00:00

  • BOF: a novel family of bacterial OB-fold proteins.

    abstract::Using top-of-the-line fold recognition methods, we assigned an oligonucleotide/oligosaccharide-binding (OB)-fold structure to a family of previously uncharacterized hypothetical proteins from several bacterial genomes. This novel family of bacterial OB-fold (BOF) proteins present in a number of pathogenic strains enco...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2004.04.086

    authors: Ginalski K,Kinch L,Rychlewski L,Grishin NV

    更新日期:2004-06-04 00:00:00

  • Substrate recognition of holocytochrome c synthase: N-terminal region and CXXCH motif of mitochondrial cytochrome c.

    abstract::Holocytochrome c synthase (HCCS) attaches heme covalently to mitochondrial respiratory cytochromes c. Little is known about the reaction of heme attachment to apocytochromes c by HCCS, although recently it has been established that the CXXCH motif and the N-terminus of the apocytochrome polypeptide are important prote...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2014.07.026

    authors: Zhang Y,Stevens JM,Ferguson SJ

    更新日期:2014-09-17 00:00:00

  • Biomolecule delivery into canola protoplasts by centrifuging cells with microbubbles.

    abstract::We have successfully delivered FITC and FITC-Dextran (70, 250 kDa) into canola protoplasts by centrifuging cells with different amounts of microbubbles at variable centrifuge speed. The efficiency is around 90%, while cell viability remains high. Confocal microscopy images show that both FITC and FITC-Dextran are scat...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2012.12.005

    authors: He C,Gu Q,Huang M,Xing J,Chen J

    更新日期:2013-01-31 00:00:00

  • Expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome-associated coronavirus.

    abstract::SARS 8b is one of the putative accessory proteins of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) with unknown functions. In this study, the cellular localization and activity of this estimated 9.6 kDa protein were examined. Confocal microscopy results indicated that SARS 8b is localized in ...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2006.05.051

    authors: Law PY,Liu YM,Geng H,Kwan KH,Waye MM,Ho YY

    更新日期:2006-06-26 00:00:00

  • How do 14-3-3 proteins work?-- Gatekeeper phosphorylation and the molecular anvil hypothesis.

    abstract::14-3-3 proteins were the first signaling molecules to be identified as discrete phosphoserine/threonine binding modules. This family of proteins, which includes seven isotypes in human cells and up to 15 in plants, plays critical roles in cell signaling events that control progress through the cell cycle, transcriptio...

    journal_title:FEBS letters

    pub_type: 杂志文章,评审

    doi:10.1016/s0014-5793(01)03288-4

    authors: Yaffe MB

    更新日期:2002-02-20 00:00:00

  • The impact of PEPC phosphorylation on growth and development of Arabidopsis thaliana: molecular and physiological characterization of PEPC kinase mutants.

    abstract::Two phosphoenolpyruvate carboxylase (PEPC) kinase genes (PPCk1 and PPCk2) are present in the Arabidopsis genome; only PPCk1 is expressed in rosette leaves. Homozygous lines of two independent PPCk1 T-DNA-insertional mutants showed very little (dln1), or no (csi8) light-induced PEPC phosphorylation and a clear retard i...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/j.febslet.2009.04.030

    authors: Meimoun P,Gousset-Dupont A,Lebouteiller B,Ambard-Bretteville F,Besin E,Lelarge C,Mauve C,Hodges M,Vidal J

    更新日期:2009-05-19 00:00:00

  • Lysine-87 is a functionally important residue in human prothymosin alpha.

    abstract::Human prothymosin alpha mutants were generated with the aid of random mutagenesis and screened for their ability to inhibit yeast Saccharomyces cerevisiae cell growth. Conversion of Lys-87 to Glu resulted in an inactivated prothymosin alpha mutant, which lost the ability of the wild-type protein to block yeast cell gr...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(96)01171-4

    authors: Rubtsov Y,Vartapetian A

    更新日期:1996-11-18 00:00:00

  • Mitochondrial Hsp78, a member of the Clp/Hsp100 family in Saccharomyces cerevisiae, cooperates with Hsp70 in protein refolding.

    abstract::The molecular chaperone protein Hsp78, a member of the Clp/Hsp100 family localized in the mitochondria of Saccharomyces cerevisiae, is required for maintenance of mitochondrial functions under heat stress. To characterize the biochemical mechanisms of Hsp78 function, Hsp78 was purified to homogeneity and its role in t...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(00)02423-6

    authors: Krzewska J,Langer T,Liberek K

    更新日期:2001-01-26 00:00:00

  • Molecular dynamics simulation of four-alpha-helix bundles that bind the anesthetic halothane.

    abstract::The mutation of a single leucine residue (L38) to methionine (M) is known experimentally to significantly increase the affinity of the synthetic four-alpha-helix bundle (Aalpha(2))(2) for the anesthetic halothane. We present a molecular dynamics study of the mutant (Aalpha(2)-L38M)(2) peptide, which consists of a dime...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/s0014-5793(00)01792-0

    authors: Davies LA,Zhong Q,Klein ML,Scharf D

    更新日期:2000-07-28 00:00:00

  • Separation of gate- and channel-forming domains in the pore-forming protein of the outer membrane of Pseudomonas aeruginosa.

    abstract::The domains of the pore-forming protein responsible for the gate and channel formations were separated and identified in the outer membrane of Pseudomonas aeruginosa. The proteolytic cleavage of the 46K channel protein, protein D2, yielded two major domains with apparent M(r) of 27K and 19K. We identified the 27K poly...

    journal_title:FEBS letters

    pub_type: 杂志文章

    doi:10.1016/0014-5793(92)80826-3

    authors: Yoshihara E,Nakae T

    更新日期:1992-07-13 00:00:00