Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Design, docking, and evaluation of multiple libraries against multiple targets.

M L Lamb1, K W Burdick, S Toba

  • 1Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California, USA.

Proteins
|January 11, 2001
PubMed
Summary

We developed a computational method for designing and screening combinatorial libraries against protein families. This approach efficiently identifies promising drug candidates by optimizing substituent selection and comparing virtual molecules.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

[Study on mechanism underlying the role of <i>HLA-DRA</i> in promoting radiation-induced sinusitis].

Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery·2026
Same author

[Early warning technology for infectious disease outbreaks in primary and secondary school students based on integrating hospital visit data and monitoring data of school absence due to illness: an effectiveness analysis].

Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi·2026
Same author

[Pathogen spectrum characteristics and influencing factors of recurrent respiratory infection in children in the Shenzhen community during winter and spring].

Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi·2026
Same author

[Prevalence of <i>Schistosoma japonicum</i> infections in wild rodents in key areas during the elimination phase].

Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control·2025
Same author

[Pathogen genome databases development and application in public health].

Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi·2025
Same author

[A comparative study of gasless transoral vestibular robotic surgery and traditional open surgery for resection of thyroglossal duct cysts].

Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery·2025

Area of Science:

  • Computational chemistry
  • Drug discovery
  • Structural biology

Background:

  • Designing and screening combinatorial libraries is crucial for identifying novel drug candidates.
  • Efficiently exploring vast chemical spaces against protein targets remains a challenge.

Purpose of the Study:

  • To present a general computational approach for the design, docking, and virtual screening of multiple combinatorial libraries against protein families.
  • To validate the method's ability to predict binding modes and experimental data.

Main Methods:

  • A three-stage method involving scaffold docking, side-chain substituent selection using a 'divide-and-conquer' algorithm, and library comparison.
  • Application to three serine proteases (trypsin, chymotrypsin, elastase) and three combinatorial libraries.

Related Experiment Videos

  • Utilized a vector-based orientation filter for scaffold docking and a free-energy-based scoring procedure.

    • Main Results:

    • The scaffold docking procedure accurately reproduced crystallographic binding modes.
    • The scoring procedure successfully predicted experimental binding data for protease inhibitor mutants.
    • The method effectively discriminated between different types of virtual libraries (peptide, benzodiazepine, tetrahydroisoquinolinone).

    Conclusions:

    • The developed computational method provides an efficient and accurate approach for designing and screening combinatorial libraries.
    • The findings have significant implications for optimizing library design in drug discovery.
    • The 'divide-and-conquer' algorithm enables linear-time exploration of large substituent lists.