39th Annual Student Research Conference
Computational Analysis of Small Molecules Targeting Complement Protein 5 (C5) for Treatment of Inflammatory Disorders
Mohammed Ayan Mahmood
Dr. Bill R. Miller (A.T. Still University), Faculty Mentor
Inflammatory disorders are a leading cause of hospital mortality, often driven by dysregulation within the immune response. Complement component 5 (C5) plays a major role in terminal phase of complement cascade, where its cleavage initiates potent inflammatory signaling. Uncontrolled activation of this process is linked to sepsis and related conditions. Inhibiting C5 cleavage, particularly at the exposed Arg751 and Leu752 peptide bond, represents a promising therapeutic strategy, although no small molecule inhibitors have yet been FDA approved.
This study aimed to identify novel inhibitors using computational methods. A library of about 500,000 N phenyl N' benzylurea derivatives, selected for their relevance to complement modulation, was screened through molecular docking, with a known high potency inhibitor used as a control.
Top candidates then underwent molecular dynamics simulations and binding free energy analyses. Several compounds showed strong, stable binding comparable to the control, supporting their potential as therapeutic leads to reduce complement driven inflammation in sepsis.
Keywords: Complement component 5 (C5), Inflammatory disorders, Sepsis, Small molecule inhibitors, Molecular docking, Molecular dynamics simulations, Binding free energy, Complement cascade modulation
Topic(s):Biochemistry and Molecular Biology
Presentation Type: Oral Presentation
Session: -1
Location: MG 1098
Time: 1:00