The interference effect of two drugs, namely propranolol and amlodipine on their interaction with human serum albumin (HSA) was investigated. For this purpose, HSA-bilirubin and HSA-warfarin simulation systems were used as a model for comparison with experimental evidences. Four simulations, i.e. "HSA only", "HSA-propranolol", "HSAamlodipine" and "HSA-propranolol-amlodipine" were designed with equal proportions of drugs. A new algorithm was proposed in order to determine the residues of high affinity for binding to each drug. The new pattern is based on counting the times of drug referral to each residue during simulation. Binding sites of bilirubin and warfarin on the human serum albumin were determined in this manner; the residues in IIA and IIIA sub-domains assume high affinity for these drugs. The acquired results are in good agreement with experimental findings. To study the mutual drug effects, the binding sites of propranolol and amlodipine on protein were determined separately and in presence of both drugs. The obtained results indicated that in absence of drug interference, the number of residues having affinity for propranolol is larger than that for amlodipine; the number of residues having affinity to propranolol considerably decreases in amlodipine presence. The protein secondary and tertiary structure changes were compared in presence and absence of drugs for interpreting the obtained results

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