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Table 1 Calculation of LGFEs of JY-1-106

From: The novel BH3 α-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xL and Mcl-1 protein–protein interactions with Bak

Total LGFEs Minimized Langevin dynamics Explict solvent MD
Bcl-xL     
  F -10.2 (4.3) -10.6 (4.2) -13.8 (4.1)
  B -10.1 (3.9) -10.6 (4.0) -15.8 (2.7)
Mcl-1      
  F -7.3 (2.9) -7.2 (2.3) -8.7 (1.5)
  B -7.8 (3.9) -7.0 (2.2) -7.5 (2.2)
Difference, Mcl-1 - Bcl-xL
  F 2.9 3.4 5.1
  B 2.3 3.6 8.3
Group contributions Minimized Langevin dynamics Explict Solvent MD
   Aromatic Aliphatic Aromatic Aliphatic Aromatic Aliphatic
Bcl-xL        
  F -6.8 -3.4 -5.9 -4.4 -11.3 -2.5
  B -7.1 -3.0 -7.2 -3.3 -12.4 -3.5
Mcl-1        
  F -4.7 -2.5 -4.9 -2.2 -4.0 -4.7
  B -4.6 -3.1 -5.5 -1.5 -5.3 -2.2
Difference, Mcl-1 - Bcl-xL
  F 2.1 0.9 1.0 2.2 7.3 -2.2
  B 2.5 -0.1 1.7 1.8 7.1 1.3
  1. Total Ligand Grid Free Energies (LGFE, kcal/mol) for JY-1-106 binding to Bcl-xL and Mcl-1 based on the minimization, Langevin Dynamics and Explicit Solvent MD simulation approaches along with LGFE group contributions summed over the aromatic and aliphatic functional groups for Bcl-xL and Mcl-1.
  2. Results are presented for both forward (F) and backward (B) orientations of JY-1-106 and differences (Mcl-1 – Bcl-xL) are presented for all values. Values in paranthesis for the total LGFEs are standard errors.