A detailed computational model of synaptic plasticity-related intracellular signalling pathways was used to investigate the molecular mechanisms of long-term potentiation (LTP) in a spine head of a hippocampal CA1 pyramidal neuron. The biochemical model can be used to study the mechanisms of different forms of plasticity, the roles and contributions of the molecular pathways, individual molecular species, and the effects of different induction protocols and various types of neuromodulations. The goal of the present study is to describe the molecular changes underlying different forms of synaptic modification and to explain a diverse set of experimental data in a unified framework.The model contains the main postsynaptic signalling pathways that take part in the formation, maintenance, and expression of hippocampal LTP: the CaMKII, the PKA and the PKC cascades. The activation of the subcellular cascades results in altered total AMPA receptor conductance which can be used as a measure of synaptic changes. Parameters of the model were fit to experimental data from hippocampal Schaffer collateral synapses. The parameters were optimized with the Neuroptimus software tool using the Neuroscience Gateway (NSG) which enables access and usage of high-performance supercomputers.After an in-depth analysis of the fitted models, different components were identified that shape LTP. These components act on different timescales using various mechanisms mediated by the interactions of the biochemical cascades. According to our predictions, the baseline ratio of different AMPA receptor subunits has a large influence on the molecular mechanisms that are utilized by the synapse to express LTP.