High load average on MySQL server

Recently we're experiencing serious performance problem on our MySQL server. Application server and database server are separate. At the database server end, load average getting higher in no time. CPU usage remain high too (around 200%).

load average: 16.91, 21.48, 30.91

At the application end we've manually closed the database connections wherever they have manually opened. my.cnf is also a bit configured using following parameters:

innodb_buffer_pool_size = 4G
query_cache_type        = 1
wait_timeout            = 1800

key_buffer              = 16M
max_allowed_packet      = 16M
thread_stack            = 192K
thread_cache_size       = 32


query_cache_limit       = 5M
query_cache_size        = 640M
query_cache_type        = 1

But still there's no visible improvement. Server usage is still very high. What could possibly go wrong with configuration? How to keep server load average normal (or at least close to normal)?

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