Prev. Article Next Article Table of Contents

Article

Binding of Aminoglycoside Antibiotics to the Small Ribosomal Subunit: A Continuum Electrostatics Investigation

Supporting Info

Chiansan Ma,^† Nathan A. Baker,*^‡ Simpson Joseph,^§ and J. Andrew McCammon

Contribution from the Department of Chemistry, Yale University, New Haven, Connecticut 06520, and Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, and Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093

J. Am. Chem. Soc., 2002, 124 (7), pp 1438–1442

DOI: 10.1021/ja016830+

Publication Date (Web): January 25, 2002

†

Yale University. E-mail: chiansan@yale.edu.

To whom correspondence should be addressed.

‡

Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, UCSD, Mail Code 0365. E-mail: nbaker@mccammon.ucsd.edu.

Department of Chemistry and Biochemistry, UCSD, Mail Code 0314. E-mail: sjoseph@ucsd.edu.

Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, and Department of Pharmacology, UCSD, Mail Code 0365. E-mail: jmccammon@ucsd.edu.

Abstract

The binding of paromomycin and similar antibiotics to the small (30S) ribosomal subunit has been studied using continuum electrostatics methods. Crystallographic information from a complex of paromomycin with the 30S subunit was used as a framework to develop structures of similar antibiotics in the same ribosomal binding site. Total binding energies were calculated from electrostatic properties obtained by solution of the Poisson−Boltzmann equation combined with a surface area-dependent apolar term. These computed results showed good correlation with experimental data. Additionally, calculation of the ribosomal electrostatic potential in the paromomycin binding site provided insight into the electrostatic mechanisms for aminoglycoside binding and clues for the rational design of more effective antibiotics.

View: Full Text HTML | Hi-Res PDF