Conformational Analysis of the 20 Naturally Occurring Amino Acid Residues Using ECEPP

Zimmerman, S. Scott; Pottle, Marcia S.; Némethy, George; Scheraga, Harold A.

doi:10.1021/ma60055a001

Cited by 712 publications

(545 citation statements)

References 5 publications

Supporting

Mentioning

514

Contrasting

Order By: Relevance

“…The sampled conformations were grouped into three classes in terms of the ($, v) region of the Gly residue [14]. This classification is consistent with a cluster analysis of RGD conformations in terms of the root-mean square deviation, because the conformation is mostly determined by the ($I, v) angles of Gly.…”

Section: Ciassijcation Of the Sampled Conformationssupporting

confidence: 76%

See 1 more Smart Citation

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃

Yamada

Kidera

1996

FEBS Letters

View full text Add to dashboard Cite

A mutant of echistatin, a disintegrin with a high affinity for the integrins, was constructed by substituting CRGDC for ARGDIJ in the Arg-Gly-Asp (RGD) region. The mutant was chemically synthesized, subjected to a folding process with air oxidation, and purified by reverse-phase HPLC. The peptide mapping and mass spectrometric analyses revealed that the two Cys residues introduced in the mutant are linked to each other, without any effect on the mode of the four disultide bonds present in native ecblstatin, as expected. The mutant strongly inhibited the binding of human fibrinogen to its receptor, integrin aIn,p3, with an I&, value of 0.12 nM. This value shows that the mutant is twice as potent as the native form (IQ, = 0.23 &I). These results indicate that the native disintegrin molecule, which has been considered to possess the optimum affinity for the integrins, can be tailored to exhibit even higher affinity by introducing the conformational constraint into the RGD region. Monte Carlo simulations of KRCRGDCMD, the RGD region in the mutant, suggested that the disulfide bond constrains the RGD region to assume a type II' p-turn, with Gly and Asp in positions 2 and 3 of the turn.

show abstract

Section: Ciassijcation Of the Sampled Conformationssupporting

confidence: 76%

“…When digested by endoproteinase Lys-C, peptide fragment L (see Fig. 2B), lacking FLK (residues [13][14][15] and GPAT (residues 4&49), was isolated by reversephase HPLC. Fragment L from the mutant was further treated with BrCN, resulting in the formation of fragment B-I, RCRGDCM (Fig.…”

Section: Resultsmentioning

confidence: 99%

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃

Yamada

Kidera

1996

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…14, and the capital letters in these symbols have been defined in Ref. 37. Table I lists the structural data of seven states of the trans proline conformations in the gas phase.…”

Section: G Comparison With the Qm Calculationsmentioning

confidence: 99%

The puckering free-energy surface of proline

2013

AIP Advances

View full text Add to dashboard Cite

Proline has two preferred puckering states, which are often characterized by the pseudorotation phase angle and amplitude. Although proline's five endocyclic torsion angles can be utilized to calculate the phase angle and amplitude, it is not clear if there is any direct correlation between each torsion angle and the proline-puckering pathway. Here we have designed five proline puckering pathways utilizing each torsion angle χj (j = 1∼5) as the reaction coordinate. By examining the free-energy surfaces of the five puckering pathways, we find they can be categorized into two groups. The χ2 pathway (χ2 is about the Cβ—Cγ bond) is especially meaningful in describing proline puckering: it changes linearly with the puckering amplitude and symmetrically with the phase angle. Our results show that this conclusion applies to both trans and cis proline conformations. We have also analyzed the correlations of proline puckering and its backbone torsion angles ϕ and ψ. We show proline has preferred puckering states at the specific regions of ϕ, ψ angles. Interestingly, the shapes of ψ-χ2 free-energy surfaces are similar among the trans proline in water, cis proline in water and cis proline in the gas phase, but they differ substantially from that of the trans proline in the gas phase. Our calculations are conducted using molecular simulations; we also verify our results using the proline conformations selected from the Protein Data Bank. In addition, we have compared our results with those calculated by the quantum mechanical methods

show abstract

“…Because of a high content of helical structure in the united-residue structures, more than 2/3 of the peptide groups participated in the dipole-path network. It is, therefore, very likely that the initial conformational states of at least that fraction of residues were located either in the correct or neighboring (9, $) regions of Zimmerman et al (1977) (Liwo et al, 1993). Then, EDMC simulations with the use of the hybrid force field were carried out on each of the five hybrid-chain structures, using the algorithm described above (section on Refinement of peptide-group orientation).…”

Section: Conversion Of United-residue Structures To All-atom Backbonementioning

confidence: 99%

“…The all-atom EDMC simulations were carried out on either a Stardent 3000 or an IBM 3090 supercomputer, making use of full vectorization of the code for the IBM computations. A total of 2,OOO-4,500 cording to Zimmerman et al (1977).…”

Section: Computational Detailsmentioning

confidence: 99%

Prediction of protein conformation on the basis of a search for compact structures: Test on avian pancreatic polypeptide

et al. 1993

View full text Add to dashboard Cite

Based on the concept that hydrophobic interactions cause a polypeptide chain to adopt a compact structure, a method is proposed to predict the structure of a protein. The procedure is carried out in four stages: (1) use of a virtual-bond united-residue approximation with the side chains represented by spheres to search conformational space extensively using specially designed interactions to lead to a collapsed structure, (2) conversion of the lowest-energy virtual-bond united-residue chain to one with a real polypeptide backbone, with optimization of the hydrogen-bond network among the backbone groups, (3) perturbation of the latter structure by the electrostatically driven Monte Carlo (EDMC) procedure, and (4) conversion of the spherical representation of the side chains to real groups and perturbation of the whole molecule by the EDMC procedure using the empirical conformational energy program for peptides (ECEPP/2) energy function plus hydration. Application of this procedure to the 36-residue avian pancreatic polypeptide led to a structure that resembled the one determined by X-ray crystallography; it had an a-helix starting at residue 13, with the N-terminal portion of the chain in an extended conformation packed against the a-helix. Similar structures with slightly higher energies, but looser packing, were also obtained.Keywords: compact conformations; conversion from a united-residue representation to an all-atom chain; hydrophobic-residue packing; Monte Carlo methods; multiple-minima problem; potential of mean force; protein folding; united-residue representation of a polypeptide chain In our continuing effort to surmount the multiple-minima problem (Scheraga, 1989;Kostrowicki & Scheraga, 1992;Olszewski et al., 1992) in computing the structure of a protein, we have developed a procedure that takes advantage of the fact that the protein core tends to consist of tightly packed nonpolar residues, with the polar ones located on the surface (Kauzmann, 1959;Rackovsky & Scheraga, 1977;Richards, 1977;Wertz & Scheraga, 1978;Chan & Dill, 1990;. Such an example of selforganization is reminiscent of early work by Onsager (1949) on the packing of tobacco mosaic virus particles and by Flory (1956) on the packing of rodlike polymers (including a-helices). These workers showed that, as the solution concentration increases, the system separates into two phases, an organized ordered one and a more dilute isotropic one. The self-organization of the moreconcentrated ordered phase arises solely from entropic effects; i.e., in a concentrated solution it is easier to pack rods in an ordered anisotropic array than in a disordered isotropic one. Of course, while entropy alone can account for this phenomenon, possible attractive interactions between the ordered rods can also contribute to this selforganization. We thus consider the possibility that, if the available conformational space of a polypeptide is confined, organized structure will be promoted.

show abstract

Conformational Analysis of the 20 Naturally Occurring Amino Acid Residues Using ECEPP

Cited by 712 publications

References 5 publications

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃

The puckering free-energy surface of proline

Prediction of protein conformation on the basis of a search for compact structures: Test on avian pancreatic polypeptide

Contact Info

Product

Resources

About

Conformational Analysis of the 20 Naturally Occurring Amino Acid Residues Using ECEPP

Cited by 712 publications

References 5 publications

Tailoring echistatin to possess higher affinity for integrin αIIbβ3

Tailoring echistatin to possess higher affinity for integrin αIIbβ3

The puckering free-energy surface of proline

Prediction of protein conformation on the basis of a search for compact structures: Test on avian pancreatic polypeptide

Contact Info

Product

Resources

About

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃

Tailoring echistatin to possess higher affinity for integrin α_IIbβ₃