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Volumn 305, Issue 5690, 2004, Pages 1605-1609

Hydrophobic collapse in multidomain protein folding

Author keywords

[No Author keywords available]

Indexed keywords

COMPUTER SIMULATION; DEWATERING; ELECTROSTATICS; HYDROPHOBICITY; MOLECULAR DYNAMICS; PARAFFINS; VAN DER WAALS FORCES;

EID: 4644236471     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.1101176     Document Type: Article
Times cited : (486)

References (33)
  • 5
  • 6
    • 0038446327 scopus 로고    scopus 로고
    • P. Ball, Nature 423, 25 (2003).
    • (2003) Nature , vol.423 , pp. 25
    • Ball, P.1
  • 9
    • 0037453597 scopus 로고    scopus 로고
    • R. Steitz et al., Langmuir 19, 2409 (2003).
    • (2003) Langmuir , vol.19 , pp. 2409
    • Steitz, R.1
  • 24
    • 4644321527 scopus 로고    scopus 로고
    • note
    • + counterions are added to make the system electrically neutral. The solvated protein systems have up to 42,000 atoms (the actual size varies for different interdomain distances). The GROMACS simulation package is used here for this large system because of its fast speed (25). Each NPT MD simulation [(26), 1 atm and 300 K] is run in parallel with 8 to 16 processors on IBM 5P2-Power3-375 MHz clusters. The OPLSAA force field is used for the protein (27), and a simple point charge (SPC) water model is used for the explicit solvent. For the long-range electrostatic interactions, the particle-mesh Ewald method is used. For the van der Waals interactions, a typical 10 Å cutoff is used. A time step of 2.0 fs is used with bond lengths constrained. A standard equilibration procedure, which includes a conjugate gradient minimization and a 100-ps MD simulation with position restraints, is followed to equilibrate each solvated system. The final configurations from equilibration are then used for data collection. We have modified GROMACS to allow us to selectively turn off certain terms in the force field, in particular, the protein-water electrostatic potential, the attractive part of the protein-water van der Waals potential, the domain-domain electrostatic potential, and the attractive part of the domain-domain van der Waals potential. This approach allows us to make a sensitivity analysis of hydrophobic collapse and to compare the protein collapse with what is already known about the hydrophobic collapse of the plates.
  • 26
    • 4644267837 scopus 로고    scopus 로고
    • note
    • One caveat is that NPT MD introduces fictitious dynamics from both the temperature and pressure control. New fictitious degrees of freedom are introduced, with corresponding kinetic energies, fictitious masses, and fictitious frequencies. These influence the time scales and can affect the rate processes observed. Nevertheless, the thermodynamic equilibrium water densities inside the interplate or interdomain region and the water depletion or dewetting phenomena should stay the same. Our observations about kinetics are borne out in careful studies.
  • 28
    • 4644340129 scopus 로고    scopus 로고
    • note
    • The original total interdomain distance is about 1B.8 Å, so after the enlargement, the total interdomain distance is about 22.8 Å. For simplicity, we will refer to it as interdomain gap distance D = 4 Å in the following.
  • 29
    • 4644369672 scopus 로고    scopus 로고
    • note
    • It is tricky to define the water density inside the domain gap region, particularly for cases with very small D values, because the fluctuation in the number of water molecules can be fairly large compared with the total number of water molecules inside the region. In general, it is very difficult to directly measure the volume inside the domain gap region because of the irregularity of the protein domain structures; thus, we used a comparative way to measure the water density.
  • 32
    • 4644349394 scopus 로고    scopus 로고
    • note
    • Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
  • 33
    • 4644267382 scopus 로고    scopus 로고
    • note
    • This work was partially supported by a grant to B.J.B. from NIH (GM4330) and a Shared University Research (SUR) grant from the IBM Corporation to Columbia University.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.